Systems and methods related to the treatment of pain with a peripheral nerve stimulation system designed to target nerves along the spine

Abstract

The present invention provides a method to reduce pain using electrical stimulation of peripheral nerves in or near the spine. This approach involves an electrical stimulation device including at least one electrode adapted for insertion within a human body and at least one pulse generator operatively coupled with the at least one electrode, wherein the pulse generator delivers electrical stimulation activating at least one peripheral nerve in or near the spine, such as the dorsal rami and its distal branches (e.g., the medial branch nerves, cluneal nerves), the ventral rami and its distal branches (e.g., sacral nerves, gluteal nerves), and those accessed via the paravertebral space (e.g., peripheral spinal nerves), to produce pain relief.

Description

Inventors: Joseph W. BoggsMeredith J. McGee William H. Clark Claire A. Zum Nathan D. CrosbyTITLESYSTEMS AND METHODS RELATED TO THE TREATMENT OF PAIN WITH A PERIPHERAL NERVE STIMULATION SYSTEM DESIGNED TO TARGET NERVES ALONG THE SPINECROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The application claims priority to U.S. Provisional Patent Application No. 63 / 523,125, filed on June 26, 2023, entitled “SYSTEMS AND METHODS RELATED TO THETREATMENT OF NECK PAIN,” which is incorporated herein by reference in its entirety.FIELD OF INVENTION

[0002] The present application generally relates to a system, device, method, and instructions for use of systems, devices, and methods to deliver electrical stimulation to relieve pain in areas of the body innervated by peripheral nerves in or near the spine, such as the dorsal rami and its distal branches (e.g., the medial branch nerves, cluneal nerves), the ventral rami and its distal branches (e.g., sacral nerves, gluteal nerves), and those accessed via the paravertebral space (e.g., peripheral spinal nerves).BACKGROUND

[0003] Chronic pain is a significant concern for millions of people in the US and around the world, causing disability by affecting daily life and normal activities. Pain is often classified into three broad categories: nociceptive pain (e.g., pain from damage or injury to bodily tissues), neuropathic pain (e.g., pain originating from nerves themselves, often as a result of injury to nerves), and nociplastic pain (e.g., when no injury to the nerves or other bodily tissuescan be identified, but nonetheless altered pain perception is present). All three types can lead to the development of chronic pain and result in mixed pain conditions (e.g., where pain has elements of both nociceptive and neuropathic pain) and central sensitization (e.g., modified / maladaptive central pain processing). Although pain may originate from anatomical lesions (e.g., herniated intervertebral discs) or damage to soft tissues (e.g., muscles), chronic spine pain, whether in the back or neck, is nonspecific (unknown cause of pain) in a majority of cases. The complexity of the underlying pain conditions often makes effective treatment challenging.

[0004] Present treatments for spine pain seldom provide adequate relief; carry risks of side effects and complications; and / or are invasive. There remains room and a need in the art of pain management for alternative systems and methods, in particular those that are minimally invasive and reversible, to be used in the treatment pain.SUMMARY

[0005] The present invention provides a system, device, method, and instructions for use of systems, devices, and methods comprising electrical stimulation from at least one lead (e.g., electrode) adapted for insertion within a human body and at least one pulse generator operatively coupled with the at least one lead, wherein the pulse generator delivers electrical stimulation activating at least one nerve (e.g., peripheral nerve, nerve trunks, or branches) or combinations of nerves in, around, or near regions of the spine (i.e., also known as the vertebral column, spinal column, backbone, or posterior trunk), such as the dorsal rami and its distal branches (e.g., the medial branch nerves, cluneal nerves), the ventral rami and its distal branches (e.g., sacral nerves, gluteal nerves), the paravertebral space (e.g., peripheral spinal nerves), that are outside of but also in proximity to, near, or adjacent to the spine (e.g., at the cervical, thoracic, lumbar, sacral, or any other level) to result in relief of pain in a desired region.

[0006] The present invention also provides a system, device, method, and instructions for use of systems, devices, and methods comprising electrical stimulation from at least one electrode adapted for insertion below the skin of a human body with spine pain or will have spine pain (e.g., is preparing for surgery near the spine and will need to manage pain afterward) and a pulse generator operatively coupled with at least one electrode, wherein the pulse generator delivers electrical stimulation for a prescribed period of time to activate at least one peripheral nerve (e.g., afferent, efferent, or mixed-type fibers) near the spine (e.g., neck, upper back, middle back, lower back) for pain relief in a desired pain region. In an embodiment, the electrical stimulation device is operatively coupled to an external stimulator operatively coupled to an external controller and / or operatively coupled to an internally implanted stimulator that is operatively coupled to an external controller.

[0007] The present invention further provides a system, device, method, and instructions for use of systems, devices, and methods to alleviate pain including placing at least one electrode within a tissue of a human body and applying stimulation through the at least one electrode to activate at least one peripheral nerve innervating a portion of the painful region (e.g., the neck, back, trunk, or extremities) to generate pain relief. Further alleviation of pain may also occur in regions not directly innervated by the peripheral nerve being activated by the at least one electrode.

[0008] The present invention also provides a system, device, method, and instructions for use of systems, devices, and methods of use of leads designed to reversibly change lead-shape in one or more dimensions in response to forces applied on the lead, which are configured for insertion into a portion of the body such that the longitudinal axis of the lead is sufficiently aligned with the direction of net force and movement by the musculoskeletal system, to avoid lead fracture or migration to prevent interruption of therapeutic delivery of electrical stimulation to a nerve (FIG. 1).

[0009] In an embodiment, the system, device, and method include modulating central neural processing through the activation of the nerve near the dorsal ramus of the human body. The method may include activating at least one paraspinal muscle of the human body through the activation of the at least one nerve near the dorsal root of the human body. The activation of the paraspinal muscle may not affect the strength of the paraspinal muscle.

[0010] The method may also produce an increase in stimulation-evoked neural encoded signals. The method may also produce a change in afferent and / or efferent nerve activity.

[0011] The method may also include evaluating an area of pain in or around the spine, positioning, repositioning, and stimulating the electrode. The method may result in the alleviation of pain in or around the spine after the stimulation is discontinued.

[0012] In one embodiment, the method may further include the insertion of additional electrodes, stimulating through the additional electrodes and comparing the results. The method may also include the removal of the original electrode and use of the additional electrodes.

[0013] Disclosed is a method of peripheral nerve stimulation. In an embodiment, the method may comprise inserting a lead into a musculoskeletal system body region; causing a reversibly change in a shape of the lead in one or more dimensions in response to forces applied on the lead; orienting the lead such that a longitudinal axis of the lead is aligned with a direction of a net force and movement by the musculoskeletal system body region; avoiding lead fracture or migration of the lead; and preventing interruption of therapeutic delivery of electrical stimulation to a nerve through the lead.

[0014] In an embodiment, the method may comprise operatively coupling an electrical stimulation device to the lead and applying electrical stimulation via the electrical stimulation device through the lead. In an embodiment, the lead may comprise one or more electrodes integrally formed on the lead, wherein the one or more electrodes are positioned proximal to a region of pain and configured to deliver electrical stimulation to at least one nerve or nervebranch that innervates the region of pain. In accordance with an embodiment, the electrical stimulation selectively activates target nerve fibers in the at least one nerve.

[0015] In an embodiment, the method may comprise the activation of target nerve fibers producing tingling sensations in the region of pain. In an embodiment, the tingling sensations may comprise paresthesia or muscle activation. In an embodiment, the lead may be oriented to position the one or more electrodes remote from the nerve. The at least one nerve comprises one or more of: spinal nerves, spinal nerve roots, medial, lateral, or other branches of dorsal or ventral rami, gluteal nerve and branches, cluneal nerve and branches, superior cluneal nerve and branches, middle cluneal nerves and branches, occipital nerves and branches rami communicantes, sympathetic chain, and / or dorsal root ganglion.

[0016] In an embodiment, at least one nerve is targeted in a paravertebral space. In an embodiment, at least one nerve is targeted in a spinal region but outside a paravertebral space. In an embodiment, at least one nerve lies in cervical, thoracic, lumbar, and / or sacral spinal regions.

[0017] In an embodiment, selective activation of target nerve fibers modulates central neural processing. In an embodiment, modulation of central neural processing provides pain relief by reconditioning maladaptive pain processing in CNS. In an embodiment, the reconditioning of maladaptive pain processing occurs during a temporary stimulation treatment period without use of a permanently implanted lead. In an embodiment, the reconditioning of maladaptive pain processing during a temporary stimulation treatment period produces durable pain relief that outlasts a stimulation treatment period. In an embodiment, modulation of central neural processing is achieved without blocking transmission of neural signals from a periphery.

[0018] In an embodiment, pain relief is produced without or without requiring targeted or regenerative changes in stability of a spine, musculature, or connective tissues. In an embodiment, pain relief is produced without providing or requiring mechanical stability. In anembodiment, pain relief is produced without directly strengthening, rehabilitating, or stabilizing, or requiring strengthening, rehabilitation, or stabilization of paraspinal muscles. In an embodiment, pain relief is produced without or without requiring functional improvement. In an embodiment, pain relief is produced without functional improvement.

[0019] In an embodiment, the lead is aligned with force-producing structures of a musculoskeletal system to minimize forces produced by muscle, connective tissue, or other tissues. In an embodiment, the lead is aligned with a force vector of a muscle it passes through. In an embodiment, the lead is placed in or near a midbelly of a muscle and avoids a boundary of the muscle. In an embodiment, the lead passes through more than one muscle and is oriented to be in line with a muscle that produces a highest force relative to any other muscles the lead passes. In an embodiment, placement of the lead does not align with a force vector of the muscle it passes through. In an embodiment, the lead is placed substantially parallel to a forceproducing structure of a musculoskeletal system to avoid shearing forces, bending forces, compressive forces, and tensile forces.

[0020] In an embodiment, the lead is placed such that a longitudinal axis of the lead is within 30 degrees of parallel to a net force vector of the muscles that the lead intersects. In an embodiment, the lead is placed such that a longitudinal axis of the lead is within 30 degrees parallel to direction of motion of the muscles that the lead intersects.

[0021] In an embodiment, the reversibility of changes in shape of the lead is conferred by at least one elastic portion of the lead that is configured to stretch and return to its original shape in response to forces placed on it by surrounding tissues. In an embodiment, the lead is placed such that an elastic portion of the lead is within 30 degrees parallel to a net force vector of the muscles that the lead intersects. In an embodiment, placement of the lead is such that an elastic portion of the lead is within 30 degrees parallel to direction of motion of the muscles that the lead intersects.

[0022] In an embodiment, orientation of the lead minimizes a difference between an angle of trajectory of the lead and an angle of the muscles that the lead intersects. In an embodiment, orientation of the lead orientation minimizes a number of muscles intersected by the lead. In an embodiment, orientation of the lead orientation minimizes tensile forces, shear forces, compressive forces, and / or bending forces acting on the lead.

[0023] In an embodiment, the lead is aligned with a musculoskeletal system to minimize damage to the lead from detrimental effects of muscle bulging, muscle rotation, muscle gearing, or combinatory effects from an interaction between the muscles and other structures. In an embodiment, orientation of the lead avoids contact with sensitive structures. In an embodiment, orientation of the lead avoids contact with epidural space, arteries, and direct contact with nerves. In an embodiment, orientation of the lead avoids contact with bony structures. In an embodiment, orientation of the lead avoids impact of muscle forces and movement maintaining a desired therapeutic distance away from the nerve.

[0024] In an embodiment, a biophysical model prescribes an alignment of the lead relative to a muscle, fascial planes, or other tissue structures or planes through which the lead passes or within which the lead is placed. In an embodiment, an orientation of the lead enables percutaneous lead placement wherein a skin exit site and required bandage are located at a predetermined location. In an embodiment, the predetermined bandage location is above buttocks and below hairline. In an embodiment, the predetermined bandage location is above a waistband of clothing worn on the body.

[0025] In an embodiment, orientation of the lead enables percutaneous lead placement such that a placement procedure and lead exit site avoid areas sensitive to allodynia. In an embodiment, the lead reversibly changes in shape or length in response to forces in the body avoid migration, fracture, movement, or displacement of the lead. In an embodiment, a portion of the lead reversibly changes in shape or length in response to forces in the body avoidingmigration, fracture, movement, or displacement of the lead. In an embodiment, another portion of the lead is stiff and does not change shape in response to forces in the body.

[0026] In an embodiment, the lead is a flexible, open-coiled lead that coils and uncoils in one or more directions in response to changes in force and / or length. In an embodiment, interstices of the coils allow tissue ingrowth to secure the lead within the body. In an embodiment, the lead is a non-coiled lead that stretches in one or more directions in response to changes in force and / or length.

[0027] In an embodiment, the lead changes diameter in response to changes in force and / or movement. In an embodiment, the lead is percutaneous and secured to skin. In an embodiment, the lead is fully implanted wherein securement to skin is not required.

[0028] In an embodiment, orientation and path of the lead is configured so that movement of surrounding tissues causes the lead to deform in one or more planes with respect to the body. In an embodiment, the orientation and path of the lead is configured to limit undesirable deformation of the lead in one or more other planes with respect to the body.

[0029] Disclosed is a method of stimulating a peripheral nerve to provide pain relief. In an embodiment, the method may comprise percutaneously inserting a lead into a region of a body wherein the lead is aligned with a direction of net force and movement by a musculoskeletal system in the region of the body, wherein the alignment mitigates against lead fraction or migration; and prevents interruption of therapeutic delivery of electrical stimulation to a nerve.

[0030] In an embodiment, electrical stimulation is applied through an electrical stimulation device operatively coupled to the lead. In an embodiment, the lead comprises one or more electrodes integrally formed on the lead, wherein the one or more electrodes are configured to be positioned proximal to a region of pain to deliver electrical stimulation to at least one nerve or nerve branch that innervates the region of pain.

[0031] In an embodiment, the electrical stimulation selectively activates target nerve fibers in the nerve. In an embodiment, the activation of target nerve fibers produces comfortable sensations in the region of pain. In an embodiment, the comfortable sensations comprise at least one of paresthesia or muscle activation.

[0032] In an embodiment, the lead is oriented to position the one or more electrodes remote from a target nerve. In an embodiment, at least one nerve comprises spinal nerves, spinal nerve roots, medial, lateral, or other branches of a dorsal or ventral rami, gluteal nerve and branches, cluneal nerve and branches, superior cluneal nerve and branches, middle cluneal nerves and branches, occipital nerves and branches rami communicantes, sympathetic chain, or dorsal root ganglion. In an embodiment, at least one nerve is targeted in a paravertebral space. In an embodiment, at least one nerve is targeted in a spinal region but outside a paravertebral space. In an embodiment, at least one nerve lies in cervical, thoracic, lumbar, and / or sacral spinal regions.

[0033] In an embodiment, the selective activation of target nerve fibers modulates central neural processing. In an embodiment, the modulation of central neural processing provides pain relief by reconditioning maladaptive pain processing in a CNS. In an embodiment, reconditioning of maladaptive pain processing occurs during a temporary stimulation treatment period without use of a permanently implanted lead.

[0034] In an embodiment, reconditioning of maladaptive pain processing during a temporary stimulation treatment period produces durable pain relief that outlasts the temporary stimulation treatment period. In an embodiment, modulation of central neural processing is achieved without requiring blocking of transmission of neural signals from a periphery.

[0035] In an embodiment, pain relief is produced without targeted or regenerative changes in stability of a spine, musculature, or connective tissues. In an embodiment, pain relief is produced without providing mechanical stability. In an embodiment, pain relief is producedwithout directly strengthening, rehabilitating, or stabilizing paraspinal muscles. In an embodiment, pain relief is produced without functional improvement.

[0036] In an embodiment, the lead is aligned with force-producing structures in a musculoskeletal system to minimize forces produced by muscle, connective tissue, or other tissues. In an embodiment, the lead is aligned with a force vector of the muscle it passes through. In an embodiment, the lead is placed in or near a midbelly of the muscle and avoids a boundary of the muscle. In an embodiment, the lead passes through more than one muscle and is oriented to be in line with a muscle that produces a highest force. In an embodiment, placement of the lead does not align with a force vector of the muscle it passes through but is aligned while navigating other issues. In an embodiment, the lead is placed generally parallel to a force-producing structure of the musculoskeletal system to avoid shearing forces, bending forces, compressive forces, and tensile forces.

[0037] In an embodiment, the lead is placed wherein a longitudinal axis of the lead is within 30 degrees parallel to a net force vector of the muscles that the lead intersects. In an embodiment, the lead is placed wherein a longitudinal axis of the lead is within 30 degrees parallel to direction of motion of the muscles that the lead intersects.

[0038] In an embodiment, the lead is orientated to minimize a difference between an angle of a lead trajectory and an angle of the muscles that the lead intersects. In an embodiment, the lead is orientated to minimize a number of muscles intersected by the lead. In an embodiment, the lead is orientated to minimize a tensile forces, shear forces, compressive forces, and / or bending forces acting on the lead.

[0039] In an embodiment, minimization of tensile, shear, compressive, and / or bending forces increases a lifespan of the lead. In an embodiment, minimization of tensile, shear, compressive, and / or bending forces increase a lifespan of the lead by avoiding lead fracture. In an embodiment, the lead is aligned with a musculoskeletal system to minimize damage to the leadfrom detrimental effects of muscle bulging, muscle rotation, muscle gearing, or combinatory effects from an interaction between muscles and other structures.

[0040] In an embodiment, the lead orientation avoids contact with sensitive structures. In an embodiment, the lead orientation avoids contact with bony structures. In an embodiment, orientation of the lead avoids an impact of muscle forces and movement that would displace the one or more electrodes away from a target nerve. In an embodiment, results of a biophysical model prescribe alignment of the lead relative to muscles, fascial planes, or other tissue structures or planes through which the lead passes or within which the lead is placed.

[0041] In an embodiment, the lead orientation enables percutaneous lead placement such that a skin exit site and required bandage are located at a predetermined location. In an embodiment, the predetermined location is above buttocks and below hairline. In an embodiment, the predetermined location is above a waistband of clothing worn on the body. In an embodiment, orientation of the lead enables percutaneous placement such that a lead exit site avoids areas sensitive to allodynia.

[0042] In an embodiment, the lead reversibly changes in shape or length in response to forces in the body to avoid migration, fracture, movement, or displacement of the lead. In an embodiment, at least one portion of the lead reversibly changes in shape or length in response to forces in the body to avoid migration, fracture, movement, or displacement of the lead. In an embodiment, another portion of the lead is stiff and does not change shape in response to forces in the body.

[0043] In an embodiment, the lead is a flexible, open-coiled lead that coils and uncoils in one or more directions in response to changes in force and / or length. In an embodiment, interstices of the coils allow tissue ingrowth to secure the lead within the body reducing lead migration. In an embodiment, the lead is a non-coiled lead that stretches in one or more directions inresponse to changes in force and / or length. In an embodiment, the lead changes diameter in response to changes in force and / or movement.

[0044] In an embodiment, the lead is percutaneous and secured at skin. In an embodiment, the lead is fully implanted such that securement at skin is not required. In an embodiment, the orientation and path of the lead is selected so that movement of surrounding tissues causes the lead to deform in one or more planes with respect to the body. In an embodiment, orientation and path of the lead is selected to limit deformation of the lead in one or more other planes with respect to the body. In an embodiment, the lead is placed in a highly mobile region of the body. In an embodiment, the highly mobile region of the body is a cervical spinal region.

[0045] In an embodiment, the lead is inserted into the body with an introducer needle. In an embodiment, the introducer is curved to increase a length of lead introduced under skin. In an embodiment, the introducer is curved to enable a lead trajectory to navigate anatomical features of the body.

[0046] Disclosed is a system for peripheral nerve stimulation to provide pain relief. In an embodiment, at least one lead is designed to reversibly change lead-shape in one or more dimensions in response to forces applied on the lead and the at least one lead is configured for insertion into a portion of the body such that the longitudinal axis of the lead is sufficiently aligned with the direction of net force and movement by the musculoskeletal system in the implanted bodily region to avoid lead fracture or migration to prevent interruption of therapeutic delivery of electrical stimulation to a nerve.

[0047] In an embodiment, an electrical stimulation device is operatively coupled to the one or more leads and configured to apply electrical stimulation. In an embodiment, at least one lead includes one or more electrodes integrally formed on the lead to be positioned proximal to one or more regions of pain and configured to deliver electrical stimulation to at least one nerve or nerve branch that innervates one of the region(s) of pain. In an embodiment, the electricalstimulation selectively activates target nerve fibers in the at least one nerve. In an embodiment, the activation of target nerve fibers produces comfortable sensations in the region or regions of pain. In an embodiment, the comfortable sensations include at least one of paresthesia or muscle activation.

[0048] In an embodiment, at least one lead is oriented to position the at least one electrode remote from the target nerve. In an embodiment, at least one nerve includes one or more of the following nerves in regions of the spine: spinal nerves, spinal nerve roots, medial, lateral, or other branches of the dorsal or ventral rami, gluteal nerve and branches, the cluneal nerve and branches, the superior cluneal nerve and branches, middle cluneal nerves and branches, occipital nerves and branches rami communicantes, sympathetic chain, dorsal root ganglion, or any other suitable peripheral nerve with sensory and / or motor innervation of spinal structures.

[0049] In an embodiment, at least one nerve is targeted in the paravertebral space. In an embodiment, at least one nerve is targeted in the spinal region but outside the paravertebral space. In an embodiment, at least one nerve lies in the cervical, thoracic, lumbar, and / or sacral spinal regions.

[0050] In an embodiment, the selective activation of target nerve fibers modulates central neural processing. In an embodiment, the modulation of central neural processing provides pain relief by reconditioning maladaptive pain processing in the CNS. In an embodiment, the reconditioning of maladaptive pain processing occurs during a temporary stimulation treatment period without the use of a permanently implanted lead. In an embodiment, the reconditioning of maladaptive pain processing during a temporary stimulation treatment period produces durable pain relief that outlasts the stimulation treatment period.

[0051] In an embodiment, the modulation of central neural processing is achieved without requiring blocking of transmission of neural signals from the periphery. In an embodiment,pain relief is produced without or without requiring targeted or regenerative changes in the stability of the spine, musculature, or connective tissues. In an embodiment, pain relief is produced without providing or requiring mechanical stability. In an embodiment, pain relief is produced without directly strengthening, rehabilitating, or stabilizing, or requiring strengthening, rehabilitation, or stabilization of paraspinal muscles. In an embodiment, pain relief is produced without or without requiring functional improvement. In an embodiment, the treatment of pain occurs with or without the presence of a specific disease, condition, etiology, imaging finding(s), and / or result(s) of one or more diagnostic examinations or physical tests.

[0052] In an embodiment, the lead is aligned with force-producing structures musculoskeletal system to minimize forces produced by the muscle, connective tissue, or other tissues. In an embodiment, the lead is aligned with the force vector of the muscle it passes through. In an embodiment, the lead is placed in or near the midbelly (i.e., thickest portion) of the muscle and avoids the boundary of the muscle. In an embodiment, the lead passes through more than one muscle and is oriented to be in line with the muscle which produces the most force. In an embodiment, the placement of the lead does not perfectly align with the force vector of the muscle(s) it passes through but is maximally aligned while navigating other issues and otherwise avoiding complications. In an embodiment, the lead is placed parallel or nearly parallel (within 30 degrees) to the force-producing structure of the musculoskeletal system to avoid shearing forces, bending forces, compressive forces, and tensile forces. In an embodiment, the placement of the lead is such that the longitudinal axis of the lead is within 30 degrees parallel to the net force vector of the muscles that the lead intersects. In an embodiment, the placement of the lead is such that the longitudinal axis of the lead is within 30 degrees parallel to direction of motion of the muscles that the lead intersects.

[0053] In an embodiment, the reversibility of changes in shape of the at least one lead is conferred by at least one elastic portion of the lead that is able to stretch and be returned to itsoriginal shape in response to forces placed on it by surrounding tissues. In an embodiment, the placement of the lead is such that the elastic portion of the lead is within 30 degrees parallel to the net force vector of the muscles that the lead intersects. In an embodiment, the placement of the lead is such that the elastic portion of the lead is within 30 degrees parallel to direction of motion of the muscles that the lead intersects.

[0054] In an embodiment, the lead orientation is optimized to minimize the difference between the angle of the lead trajectory and the angle of the muscles that the lead intersects. In an embodiment, the lead orientation is optimized to minimize the number of muscles intersected by the lead. In an embodiment, the lead orientation is optimized to minimize the tensile forces, shear forces, compressive forces, and / or bending forces acting on the lead.

[0055] In an embodiment, the minimization of tensile, shear, compressive, and / or bending forces increases the lifespan of the lead and avoids the need for repeat procedures to replace the lead. In an embodiment, the minimization of tensile, shear, compressive, and / or bending forces increase the lifespan of the lead by avoiding lead fracture. In an embodiment, the lead is aligned with the musculoskeletal system to minimize damage to the stimulating lead from detrimental effects of muscle bulging, muscle rotation, muscle gearing, or combinatory effects from the interaction between muscles and other structures.

[0056] In an embodiment, the lead orientation avoids contact with sensitive structures, such as epidural space, arteries, or direct contact with nerves. In an embodiment, the lead orientation avoids contact with bony structures, such as the transverse process of the spine.

[0057] In an embodiment, orientation of the at least one lead avoids the impact of muscle forces and movement that would displace the one or more electrodes away from the target nerve, thus maintaining a desired therapeutic distance away from the nerve. In an embodiment, the results of a biophysical model prescribe the alignment of the lead relative to the muscle more muscles, fascial planes, or other tissue structures or planes through which the lead passes or within whichthe lead is placed. In an embodiment, the lead orientation enables percutaneous lead placement such that the skin exit site and required bandage are located at a preferred location. In an embodiment, the preferred bandage location is above the buttocks and below the hairline. In an embodiment, the preferred bandage location is above the waistband of clothing worn on the body.

[0058] In an embodiment, the lead orientation enables percutaneous lead placement such that the placement procedure and lead exit site avoid areas sensitive to allodynia. In an embodiment, at least one lead reversibly changes in shape or length in response to forces in the body to avoid migration, fracture, movement, or displacement of the lead. In an embodiment, a portion of the lead reversibly changes in shape or length in response to forces in the body to avoid migration, fracture, movement, or displacement of the lead. In an embodiment, another portion of the lead is stiff and does not change shape in response to forces in the body.

[0059] In an embodiment, the lead is a flexible, open-coiled lead which coils and uncoils in one or more directions in response to changes in force and / or length. In an embodiment, the interstices of the coils allow tissue ingrowth to secure better the lead within the body, thereby reducing lead migration. In an embodiment, the lead is a non-coiled lead which stretches in one or more directions in response to changes in force and / or length. In an embodiment, the lead changes diameter in response to changes in force and / or movement. In an embodiment, the lead is percutaneous and secured at the skin. In an embodiment, the lead is fully implanted such that securement at the skin is not required.

[0060] In an embodiment, the orientation and path of the at least one lead is selected so that movement of surrounding tissues causes the lead to desirably deform in one or more planes with respect to the body. In an embodiment, the orientation and path of the at least one lead is selected to limit undesirable deformation of the lead in one or more other planes with respectto the body. In an embodiment, the lead is placed in a highly mobile region of the body. In an embodiment, the highly mobile region of the body is the cervical spinal region.

[0061] In an embodiment, the lead is inserted into the body with an introducer needle. In an embodiment, the introducer is curved to increase the length of lead introduced under the skin. In an embodiment, the introducer is curved to enable the lead trajectory to navigate anatomical features of the body.

[0062] Disclosed is a system for peripheral nerve stimulation to provide pain relief. In an embodiment, at least one lead is configured for insertion into a portion of the body such that the lead is sufficiently aligned with the direction of net force and movement by the musculoskeletal system in the implanted bodily region to avoid lead fraction or migration to prevent interruption of therapeutic delivery of electrical stimulation to a nerve.

[0063] In an embodiment, an electrical stimulation device is operatively coupled to the one or more leads and configured to apply electrical stimulation. In an embodiment, at least one lead includes one or more electrodes integrally formed on the lead to be positioned proximal to one or more regions of pain and configured to deliver electrical stimulation to at least one nerve or nerve branch that innervates one of the region(s) of pain. In an embodiment, the electrical stimulation selectively activates target nerve fibers in the at least one nerve. In an embodiment, the activation of target nerve fibers produces comfortable sensations in the region or regions of pain. In an embodiment, the comfortable sensations include at least one of paresthesia or muscle activation. In an embodiment, at least one lead is oriented to position the at least one electrode remote from the target nerve.

[0064] In an embodiment, at least one nerve includes one or more of the following nerves in regions of the spine: spinal nerves, spinal nerve roots, medial, lateral, or other branches of the dorsal or ventral rami, gluteal nerve and branches, the cluneal nerve and branches, the superior cluneal nerve and branches, middle cluneal nerves and branches, occipital nerves and branchesrami communicantes, sympathetic chain, dorsal root ganglion, or any other suitable peripheral nerve with sensory and / or motor innervation of spinal structures.

[0065] In an embodiment, at least one nerve is targeted in the paravertebral space. In an embodiment, at least one nerve is targeted in the spinal region but outside the paravertebral space. In an embodiment, at least one nerve lies in the cervical, thoracic, lumbar, and / or sacral spinal regions. In an embodiment, the selective activation of target nerve fibers modulates central neural processing. In an embodiment, the modulation of central neural processing provides pain relief by reconditioning maladaptive pain processing in the CNS. In an embodiment, the reconditioning of maladaptive pain processing occurs during a temporary stimulation treatment period without the use of a permanently implanted lead. In an embodiment, the reconditioning of maladaptive pain processing during a temporary stimulation treatment period produces durable pain relief that outlasts the stimulation treatment period.

[0066] In an embodiment, the modulation of central neural processing is achieved without requiring blocking of transmission of neural signals from the periphery. In an embodiment, pain relief is produced without or without requiring targeted or regenerative changes in the stability of the spine, musculature, or connective tissues. In an embodiment, pain relief is produced without providing or requiring mechanical stability. In an embodiment, pain relief is produced without directly strengthening, rehabilitating, or stabilizing, or requiring strengthening, rehabilitation, or stabilization of paraspinal muscles. In an embodiment, pain relief is produced without or without requiring functional improvement.

[0067] In an embodiment, the treatment of pain occurs with or without the presence of a specific disease, condition, etiology, imaging finding(s), and / or result(s) of one or more diagnostic examinations or physical tests. In an embodiment, the lead is aligned with forceproducing structures musculoskeletal system to minimize forces produced by the muscle, connective tissue, or other tissues. In an embodiment, the lead is aligned with the force vectorof the muscle it passes through. In an embodiment, the lead is placed in or near the midbelly (i.e., thickest portion) of the muscle and avoids the boundary of the muscle. In an embodiment, the lead passes through more than one muscle and is oriented to be in line with the muscle which produces the most force. In an embodiment, placement of the lead does not perfectly align with the force vector of the muscle(s) it passes through but is maximally aligned while navigating other issues and otherwise avoiding complications.

[0068] In an embodiment, the lead is placed parallel or nearly parallel (within 30 degrees) to the force-producing structure of the musculoskeletal system to avoid shearing forces, bending forces, compressive forces, and tensile forces. In an embodiment, the placement of the lead is such that the longitudinal axis of the lead is within 30 degrees parallel to the net force vector of the muscles that the lead intersects. In an embodiment, placement of the lead is such that the longitudinal axis of the lead is within 30 degrees parallel to direction of motion of the muscles that the lead intersects.

[0069] In an embodiment, the lead orientation is optimized to minimize the difference between the angle of the lead trajectory and the angle of the muscles that the lead intersects. In an embodiment, the lead orientation is optimized to minimize the number of muscles intersected by the lead. In an embodiment, the lead orientation is optimized to minimize the tensile forces, shear forces, compressive forces, and / or bending forces acting on the lead. In an embodiment, the minimization of tensile, shear, compressive, and / or bending forces increases the lifespan of the lead and avoids the need for repeat procedures to replace the lead. In an embodiment, the minimization of tensile, shear, compressive, and / or bending forces increase the lifespan of the lead by avoiding lead fracture.

[0070] In an embodiment, the lead is aligned with the musculoskeletal system to minimize damage to the stimulating lead from detrimental effects of muscle bulging, muscle rotation, muscle gearing, or combinatory effects from the interaction between muscles and otherstructures. In an embodiment, the lead orientation avoids contact with sensitive structures, such as epidural space, arteries, or direct contact with nerves. In an embodiment, the lead orientation avoids contact with bony structures, such as the transverse process of the spine. In an embodiment, the orientation of the at least one lead avoids the impact of muscle forces and movement that would displace the one or more electrodes away from the target nerve, thus maintaining a desired therapeutic distance away from the nerve.

[0071] In an embodiment, the results of a biophysical model prescribe the alignment of the lead relative to the muscle more muscles, fascial planes, or other tissue structures or planes through which the lead passes or within which the lead is placed. In an embodiment, the lead orientation enables percutaneous lead placement such that the skin exit site and required bandage are located at a preferred location. In an embodiment, the preferred bandage location is above the buttocks and below the hairline. In an embodiment, the preferred bandage location is above the waistband of clothing worn on the body. In an embodiment, the lead orientation enables percutaneous lead placement such that the placement procedure and lead exit site avoid areas sensitive to allodynia.

[0072] In an embodiment, the at least one lead reversibly changes in shape or length in response to forces in the body to avoid migration, fracture, movement, or displacement of the lead. In an embodiment, at least one portion of the lead reversibly changes in shape or length in response to forces in the body to avoid migration, fracture, movement, or displacement of the lead. In an embodiment, another portion of the lead is stiff and does not change shape in response to forces in the body.

[0073] In an embodiment, the lead is a flexible, open-coiled lead which coils and uncoils in one or more directions in response to changes in force and / or length. In an embodiment, the interstices of the coils allow tissue ingrowth to secure better the lead within the body, therebyreducing lead migration. In an embodiment, the lead is a non-coiled lead which stretches in one or more directions in response to changes in force and / or length.

[0074] In an embodiment, the lead changes diameter in response to changes in force and / or movement. In an embodiment, the lead is percutaneous and secured at the skin. In an embodiment, the lead is fully implanted such that securement at the skin is not required. In an embodiment, the orientation and path of the at least one lead is selected so that movement of surrounding tissues causes the lead to desirably deform in one or more planes with respect to the body. In an embodiment, the orientation and path of the at least one lead is selected to limit undesirable deformation of the lead in one or more other planes with respect to the body.

[0075] In an embodiment, the lead is placed in a highly mobile region of the body. In an embodiment, the highly mobile region of the body is the cervical spinal region. In an embodiment, the lead is inserted into the body with an introducer needle. In an embodiment, the introducer is curved to increase the length of lead introduced under the skin. In an embodiment, the introducer is curved to enable the lead trajectory to navigate anatomical features of the body.

[0076] In accordance with an embodiment, a method for peripheral nerve stimulation to provide pain relief comprises inserting at least one lead into a portion of the body, wherein the at least one lead is designed to reversibly change lead-shape in one or more dimensions in response to forces applied on the lead, and wherein the at least one lead is oriented such that the longitudinal axis of the lead is sufficiently aligned with the direction of net force and movement by the musculoskeletal system in the implanted bodily region to avoid lead fracture or migration to prevent interruption of therapeutic delivery of electrical stimulation to a nerve.

[0077] In an embodiment, an electrical stimulation device is operatively coupled to the one or more leads and applies electrical stimulation. In an embodiment, the at least one lead includes one or more electrodes integrally formed on the lead that are positioned proximal to one ormore regions of pain and configured to deliver electrical stimulation to at least one nerve or nerve branch that innervates one of the region(s) of pain. In an embodiment, the electrical stimulation selectively activates target nerve fibers in the at least one nerve. In an embodiment, the activation of target nerve fibers produces comfortable sensations in the region or regions of pain. In an embodiment, the comfortable sensations include at least one of paresthesia or muscle activation. In an embodiment, the at least one lead is oriented to position the at least one electrode remote from the target nerve.

[0078] In an embodiment, the at least one nerve includes one or more of the following nerves in regions of the spine: spinal nerves, spinal nerve roots, medial, lateral, or other branches of the dorsal or ventral rami, gluteal nerve and branches, the cluneal nerve and branches, the superior cluneal nerve and branches, middle cluneal nerves and branches, occipital nerves and branches rami communicantes, sympathetic chain, dorsal root ganglion, or any other suitable peripheral nerve with sensory and / or motor innervation of spinal structures. In an embodiment, the at least one nerve is targeted in the paravertebral space.

[0079] In an embodiment, the at least one nerve is targeted in the spinal region but outside the paravertebral space. In an embodiment, the at least one nerve lies in the cervical, thoracic, lumbar, and / or sacral spinal regions. In an embodiment, the selective activation of target nerve fibers modulates central neural processing. In an embodiment, the modulation of central neural processing provides pain relief by reconditioning maladaptive pain processing in the CNS. In an embodiment, the reconditioning of maladaptive pain processing occurs during a temporary stimulation treatment period without the use of a permanently implanted lead. In an embodiment, the reconditioning of maladaptive pain processing during a temporary stimulation treatment period produces durable pain relief that outlasts the stimulation treatment period.

[0080] In an embodiment, the modulation of central neural processing is achieved without requiring blocking of transmission of neural signals from the periphery. In an embodiment,pain relief is produced without or without requiring targeted or regenerative changes in the stability of the spine, musculature, or connective tissues. In an embodiment, pain relief is produced without providing or requiring mechanical stability. In an embodiment, pain relief is produced without directly strengthening, rehabilitating, or stabilizing, or requiring strengthening, rehabilitation, or stabilization of paraspinal muscles. In an embodiment, pain relief is produced without or without requiring functional improvement. In an embodiment, the treatment of pain occurs with or without the presence of a specific disease, condition, etiology, imaging finding(s), and / or result(s) of one or more diagnostic examinations or physical tests.

[0081] In an embodiment, the lead is aligned with force-producing structures musculoskeletal system to minimize forces produced by the muscle, connective tissue, or other tissues. In an embodiment, the lead is aligned with the force vector of the muscle it passes through. In an embodiment, the lead is placed in or near the midbelly (i.e., thickest portion) of the muscle and avoids the boundary of the muscle. In an embodiment, the lead passes through more than one muscle and is oriented to be in line with the muscle which produces the most force. In an embodiment, the placement of the lead does not perfectly align with the force vector of the muscle(s) it passes through but is maximally aligned while navigating other issues and otherwise avoiding complications. In an embodiment, the lead is placed parallel or nearly parallel (within 30 degrees) to the force-producing structure of the musculoskeletal system to avoid shearing forces, bending forces, compressive forces, and tensile forces. In an embodiment, the placement of the lead is such that the longitudinal axis of the lead is within 30 degrees parallel to the net force vector of the muscles that the lead intersects.

[0082] In an embodiment, the placement of the lead is such that the longitudinal axis of the lead is within 30 degrees parallel to direction of motion of the muscles that the lead intersects. In an embodiment, the reversibility of changes in shape of the at least one lead is conferred by at least one elastic portion of the lead that is able to stretch and be returned to its original shapein response to forces placed on it by surrounding tissues. In an embodiment, the placement of the lead is such that the elastic portion of the lead is within 30 degrees parallel to the net force vector of the muscles that the lead intersects. In an embodiment, the placement of the lead is such that the elastic portion of the lead is within 30 degrees parallel to direction of motion of the muscles that the lead intersects. In an embodiment, the lead orientation is optimized to minimize the difference between the angle of the lead trajectory and the angle of the muscles that the lead intersects. In an embodiment, the lead orientation is optimized to minimize the number of muscles intersected by the lead.

[0083] In an embodiment, the lead orientation is optimized to minimize the tensile forces, shear forces, compressive forces, and / or bending forces acting on the lead. In an embodiment, the minimization of tensile, shear, compressive, and / or bending forces increases the lifespan of the lead and avoids the need for repeat procedures to replace the lead. In an embodiment, the minimization of tensile, shear, compressive, and / or bending forces increase the lifespan of the lead by avoiding lead fracture. In an embodiment, the lead is aligned with the musculoskeletal system to minimize damage to the stimulating lead from detrimental effects of muscle bulging, muscle rotation, muscle gearing, or combinatory effects from the interaction between muscles and other structures. In an embodiment, the lead orientation avoids contact with sensitive structures, such as epidural space, arteries, or direct contact with nerves.

[0084] In an embodiment, the lead orientation avoids contact with bony structures, such as the transverse process of the spine. In an embodiment, the orientation of the at least one lead avoids the impact of muscle forces and movement that would displace the one or more electrodes away from the target nerve, thus maintaining a desired therapeutic distance away from the nerve. In an embodiment, the results of a biophysical model prescribe the alignment of the lead relative to the muscle more muscles, fascial planes, or other tissue structures or planes through which the lead passes or within which the lead is placed. In an embodiment, the lead orientationenables percutaneous lead placement such that the skin exit site and required bandage are located at a preferred location.

[0085] In an embodiment, the preferred bandage location is above the buttocks and below the hairline. In an embodiment, the preferred bandage location is above the waistband of clothing worn on the body. In an embodiment, the lead orientation enables percutaneous lead placement such that the placement procedure and lead exit site avoid areas sensitive to allodynia. In an embodiment, the at least one lead reversibly changes in shape or length in response to forces in the body to avoid migration, fracture, movement, or displacement of the lead. In an embodiment, a portion of the lead reversibly changes in shape or length in response to forces in the body to avoid migration, fracture, movement, or displacement of the lead. In an embodiment, another portion of the lead is stiff and does not change shape in response to forces in the body. In an embodiment, the lead is a flexible, open-coiled lead which coils and uncoils in one or more directions in response to changes in force and / or length.

[0086] In an embodiment, the interstices of the coils allow tissue ingrowth to secure better the lead within the body, thereby reducing lead migration. In an embodiment, the lead is a noncoiled lead which stretches in one or more directions in response to changes in force and / or length. In an embodiment, the lead changes diameter in response to changes in force and / or movement. In an embodiment, the lead is percutaneous and secured at the skin. In an embodiment, the lead is fully implanted such that securement at the skin is not required. In an embodiment, the orientation and path of the at least one lead is selected so that movement of surrounding tissues causes the lead to desirably deform in one or more planes with respect to the body. In an embodiment, the orientation and path of the at least one lead is selected to limit undesirable deformation of the lead in one or more other planes with respect to the body. In an embodiment, the lead is placed in a highly mobile region of the body.

[0087] In an embodiment, the highly mobile region of the body is the cervical spinal region. In an embodiment, the lead is inserted into the body with an introducer needle. In an embodiment, the introducer is curved to increase the length of lead introduced under the skin. In an embodiment, the introducer is curved to enable the lead trajectory to navigate anatomical features of the body. In accordance with another embodiment, a method for peripheral nerve stimulation to provide pain relief comprises insertion of at least one lead into a portion of the body such that the lead is sufficiently aligned with the direction of net force and movement by the musculoskeletal system in the implanted bodily region to avoid lead fraction or migration to prevent interruption of therapeutic delivery of electrical stimulation to a nerve. In an embodiment, an electrical stimulation device is operatively coupled to the one or more leads and applies electrical stimulation. In an embodiment, the at least one lead includes one or more electrodes integrally formed on the lead to be positioned proximal to one or more regions of pain to deliver electrical stimulation to at least one nerve or nerve branch that innervates one of the region(s) of pain.

[0088] In an embodiment, the electrical stimulation selectively activates target nerve fibers in the at least one nerve. In an embodiment, the activation of target nerve fibers produces comfortable sensations in the region or regions of pain. In an embodiment, the comfortable sensations include at least one of paresthesia or muscle activation. In an embodiment, the at least one lead is oriented to position the at least one electrode remote from the target nerve. In an embodiment, the at least one nerve includes one or more of the following nerves in regions of the spine: spinal nerves, spinal nerve roots, medial, lateral, or other branches of the dorsal or ventral rami, gluteal nerve and branches, the cluneal nerve and branches, the superior cluneal nerve and branches, middle cluneal nerves and branches, occipital nerves and branches rami communicantes, sympathetic chain, dorsal root ganglion, or any other suitable peripheral nerve with sensory and / or motor innervation of spinal structures.

[0089] In an embodiment, the at least one nerve is targeted in the paravertebral space. In an embodiment, the at least one nerve is targeted in the spinal region but outside the paravertebral space. In an embodiment, the at least one nerve lies in the cervical, thoracic, lumbar, and / or sacral spinal regions. In an embodiment, the selective activation of target nerve fibers modulates central neural processing. In an embodiment, the modulation of central neural processing provides pain relief by reconditioning maladaptive pain processing in the CNS.

[0090] In an embodiment, the reconditioning of maladaptive pain processing occurs during a temporary stimulation treatment period without the use of a permanently implanted lead. In an embodiment, the reconditioning of maladaptive pain processing during a temporary stimulation treatment period produces durable pain relief that outlasts the stimulation treatment period. In an embodiment, the modulation of central neural processing is achieved without requiring blocking of transmission of neural signals from the periphery. In an embodiment, pain relief is produced without or without requiring targeted or regenerative changes in the stability of the spine, musculature, or connective tissues. In an embodiment, pain relief is produced without providing or requiring mechanical stability. In an embodiment, pain relief is produced without directly strengthening, rehabilitating, or stabilizing, or requiring strengthening, rehabilitation, or stabilization of paraspinal muscles. In an embodiment, pain relief is produced without or without requiring functional improvement.

[0091] In an embodiment, the treatment of pain occurs with or without the presence of a specific disease, condition, etiology, imaging finding(s), and / or result(s) of one or more diagnostic examinations or physical tests. In an embodiment, the lead is aligned with forceproducing structures musculoskeletal system to minimize forces produced by the muscle, connective tissue, or other tissues. In an embodiment, the lead is aligned with the force vector of the muscle it passes through. In an embodiment, the lead is placed in or near the midbelly (i.e., thickest portion) of the muscle and avoids the boundary of the muscle. In an embodiment,the lead passes through more than one muscle and is oriented to be in line with the muscle which produces the most force. In an embodiment, the placement of the lead does not perfectly align with the force vector of the muscle(s) it passes through but is maximally aligned while navigating other issues and otherwise avoiding complications.

[0092] In an embodiment, the lead is placed parallel or nearly parallel (within 30 degrees) to the force-producing structure of the musculoskeletal system to avoid shearing forces, bending forces, compressive forces, and tensile forces. In an embodiment, the placement of the lead is such that the longitudinal axis of the lead is within 30 degrees parallel to the net force vector of the muscles that the lead intersects. In an embodiment, the placement of the lead is such that the longitudinal axis of the lead is within 30 degrees parallel to direction of motion of the muscles that the lead intersects. In an embodiment, the lead orientation is optimized to minimize the difference between the angle of the lead trajectory and the angle of the muscles that the lead intersects. In an embodiment, the lead orientation is optimized to minimize the number of muscles intersected by the lead. In an embodiment, the lead orientation is optimized to minimize the tensile forces, shear forces, compressive forces, and / or bending forces acting on the lead.

[0093] In an embodiment, the minimization of tensile, shear, compressive, and / or bending forces increases the lifespan of the lead and avoids the need for repeat procedures to replace the lead. In an embodiment, the minimization of tensile, shear, compressive, and / or bending forces increase the lifespan of the lead by avoiding lead fracture. In an embodiment, the lead is aligned with the musculoskeletal system to minimize damage to the stimulating lead from detrimental effects of muscle bulging, muscle rotation, muscle gearing, or combinatory effects from the interaction between muscles and other structures. In an embodiment, the lead orientation avoids contact with sensitive structures, such as epidural space, arteries, or direct contact with nerves.

[0094] In an embodiment, the lead orientation avoids contact with bony structures, such as the transverse process of the spine. In an embodiment, the orientation of the at least one lead avoids the impact of muscle forces and movement that would displace the one or more electrodes away from the target nerve, thus maintaining a desired therapeutic distance away from the nerve.

[0095] In an embodiment, the results of a biophysical model prescribe the alignment of the lead relative to the muscle more muscles, fascial planes, or other tissue structures or planes through which the lead passes or within which the lead is placed. In an embodiment, the lead orientation enables percutaneous lead placement such that the skin exit site and required bandage are located at a preferred location. In an embodiment, the preferred bandage location is above the buttocks and below the hairline. In an embodiment, the preferred bandage location is above the waistband of clothing worn on the body. In an embodiment, the lead orientation enables percutaneous lead placement such that the placement procedure and lead exit site avoid areas sensitive to allodynia.

[0096] In an embodiment, the at least one lead reversibly changes in shape or length in response to forces in the body to avoid migration, fracture, movement, or displacement of the lead. In an embodiment, at least one portion of the lead reversibly changes in shape or length in response to forces in the body to avoid migration, fracture, movement, or displacement of the lead. In an embodiment, another portion of the lead is stiff and does not change shape in response to forces in the body. In an embodiment, the lead is a flexible, open-coiled lead which coils and uncoils in one or more directions in response to changes in force and / or length. In an embodiment, the interstices of the coils allow tissue ingrowth to secure better the lead within the body, thereby reducing lead migration. In an embodiment, the lead is a non-coiled lead which stretches in one or more directions in response to changes in force and / or length.

[0097] In an embodiment, the lead changes diameter in response to changes in force and / or movement. In an embodiment, the lead is percutaneous and secured at the skin. In an embodiment, the lead is fully implanted such that securement at the skin is not required. In an embodiment, the orientation and path of the at least one lead is selected so that movement of surrounding tissues causes the lead to desirably deform in one or more planes with respect to the body. In an embodiment, the orientation and path of the at least one lead is selected to limit undesirable deformation of the lead in one or more other planes with respect to the body.

[0098] In an embodiment, the lead is placed in a highly mobile region of the body. In an embodiment, the highly mobile region of the body is the cervical spinal region. In an embodiment, the lead is inserted into the body with an introducer needle. In an embodiment, the introducer is curved to increase the length of lead introduced under the skin. In an embodiment, the introducer is curved to enable the lead trajectory to navigate anatomical features of the body.

[0099] Disclosed is method of peripheral nerve stimulation. In an embodiment, the method may comprise inserting a lead into a musculoskeletal system body region; causing a reversible change in a shape of the lead in one or more dimensions in response to forces applied on the lead; orienting the lead such that a longitudinal axis of the lead is aligned with a direction of a net force and movement by the musculoskeletal system body region; and preventing interruption of therapeutic delivery of electrical stimulation to a nerve through the lead.

[0100] Other features and advantages of the present inventions are set forth in the following specification and attached drawings.DESCRIPTION OF THE DRAWINGS

[0101] Operation of the present teachings may be better understood by reference to the detailed description taken in connection with the following illustrations. These appendeddrawings form part of this specification, and written information in the drawings should be treated as part of this disclosure. In the drawings:

[0102] FIG. 1A is a schematic anatomic view of the lumbar spine in the anterior- posterior view, with paraspinal muscle (e.g., multifidi) bundles (e.g., muscles, muscle fascicles, muscle fibers, muscle planes);

[0103] FIG. IB illustrates an embodiment of a lead inserted into the body in accordance with various disclosed aspects herein;

[0104] FIG. 1C shows the lead of FIG. IB when the surrounding muscle(s) are at rest in accordance with various disclosed aspects herein;

[0105] FIG. ID shows the lead of FIG. IB when the surrounding muscle(s) are in contraction in accordance with various disclosed aspects herein;

[0106] FIG. IE shows the lead of FIG. IB when the surrounding muscle(s) are elongated in accordance with various disclosed aspects herein;

[0107] FIGs. 2A and 2B are schematic anatomic views, respectively anterior and lateral, of a human peripheral nervous system;

[0108] FIG. 2C is a schematic anatomic view of a human spine, showing the various regions and the vertebrae comprising the regions;

[0109] FIGs. 2D and 2E are schematic anatomic views of the dermatome boundaries of a human;

[0110] FIGs. 2F and 2G are anatomic views of the intercostal spinal nerves of a human;

[0111] FIG. 3 illustrates non-exhaustive ways that a muscle or muscle bundle (e.g., muscle fascicle, muscle fiber, muscle plane) can change shape during activities of daily living, during movement, standing, sitting, sleeping, or during stimulation or as a result of stimulation including lengthening (FIG. 3B), constricting (FIG. 3C), bulging (FIG. 3D), shortening (FIG. 3E), twisting (FIG. 3F), and changes in angle (FIG. 3G);

[0112] FIG. 4 is a schematic representation of musculoskeletal morphology showing a myofibril, muscle fibers or cell, muscle fascicle, muscle or skeletal muscle, as exemplarily joined to a tendon and bone;

[0113] FIG. 5 illustrates non-exhaustive arrangements of fascicles within muscle, including parallel muscle fascicles (FIG. 5A), unipennate muscle fascicles (FIG. 5B), bipennate fascicles (FIG. 5C), .and / or muscles may have multipennate muscle fascicles (FIG. 5D);

[0114] FIG. 6 illustrates non-exhaustive examples of muscles with fascicles whose axis of longitudinal length change is generally parallel (FIG. 6A) to longitudinal muscle length change, is at an angle (0i, FIG. 6B) to longitudinal muscle length change, or having two muscle planes (e.g., a bipennate muscle, two separate muscles, etc.) where one plane is at an angle 0x and a second plane is at an angle 0y (FIG. 6C) to longitudinal muscle length change.

[0115] FIG. 7A shows an embodiment of a lead placed orthogonal (e.g., approximately 90-degree angle) to a longitudinal axis of movement or net force of two muscles, muscle planes, or muscle bundles (e.g., fascicles);

[0116] FIG. 7B shows the lead of FIG. 7A during a contraction, where one muscle may move, displace, bulge, constrict, contract, or lengthen more than another muscle, muscle plane, or muscle bundle;

[0117] FIG. 7C shows an embodiment of a lead that is aligned with a longitudinal axis of movement or net force of one or more muscle, muscle plane, or muscle bundle (e.g., fascicles);

[0118] FIG. 7D shows the lead of FIG. 7A during a contraction, where one muscle may move, displace, bulge, constrict, contract, or lengthen more that another muscle, muscle plane, or muscle bundle;

[0119] FIG. 8A shows a peak force generating capacity (i.e., amount of forces each muscle can produce that cause lead fracture, dislodgment, or migration) for a deep muscle and a superficial muscle;

[0120] FIGs. 8B-C show an embodiment of a lead placed perpendicular to the superficial boundary, and not aligned with either the superficial muscle or the deep muscle and the resulting forces of the muscles acting on the lead;

[0121] FIGs. 8D-E show an embodiment of a lead placed such that the longitudinal axis of the lead is aligned (e.g., parallel) to the superficial muscle, but is not aligned (e.g., orthogonal) to the deep muscle and the resulting forces of the muscles acting on the lead;

[0122] FIGs. 8F-G show an embodiment of a lead placed such that the longitudinal axis of the lead is aligned (e.g., parallel) to the deep muscle, but is not aligned (e.g., orthogonal) to the superficial muscle and the resulting forces of the muscles acting on the lead;

[0123] FIG. 9A shows a peak force generating capacity (i.e., amount of forces each muscle can produce that cause lead fracture, dislodgment, or migration) for a deep muscle and a superficial muscle;

[0124] FIGs. 9B-D show an embodiment of a lead placed perpendicular to the superficial boundary, and not aligned with either the superficial muscle or the deep muscle, the resulting forces of the muscles acting on the lead, and months of treatment to fracture;

[0125] FIGs. 9E-G show an embodiment of a lead placed such that the longitudinal axis of the lead avoids the superficial muscle, but is placed in the deep muscle, but not aligned (e.g., orthogonal) with the relative orientation of the deep muscle, the resulting forces of the muscles acting on the lead, and months of treatment to fracture;

[0126] FIGs. 9H-J show an embodiment of a lead placed such that the longitudinal axis of the lead is aligned (e.g., parallel) to the deep muscle, and avoids the superficial muscle, , the resulting forces of the muscles acting on the lead, and months of treatment to fracture;

[0127] FIG. 10A shows a peak force generating capacity (i.e., amount of forces each muscle can produce that cause lead fracture, dislodgment, or migration) for a deep muscle and a superficial muscle;

[0128] FIGs. 10B-D show an embodiment of a lead placed perpendicular to the superficial boundary, and not aligned with either the superficial muscle or the deep muscle, the resulting forces of the muscles acting on the lead, and months of treatment to fracture;

[0129] FIGs. 10E-G show an embodiment of a lead placed such that the longitudinal axis of the lead is aligned (e.g., parallel) to the superficial muscle, but is not aligned (e.g., orthogonal) to the deep muscle, the resulting forces of the muscles acting on the lead, and months of treatment to fracture;

[0130] FIGs. 10H-J show an embodiment of a lead placed such that the longitudinal axis of the lead is aligned (e.g., parallel) to the deep muscle, but is not aligned (e.g., orthogonal) to the superficial muscle, the resulting forces of the muscles acting on the lead, and months of treatment to fracture;

[0131] FIG. 11A shows a peak force generating capacity (i.e., amount of forces each muscle can produce that cause lead fracture, dislodgment, or migration) for a deep muscle and a superficial muscle;

[0132] FIGs. 11B-D show an embodiment of a lead placed perpendicular to the superficial boundary, and not aligned with either the superficial muscle or the deep muscle, the resulting forces of the muscles acting on the lead, and months of treatment to fracture;

[0133] FIGs. 11E-G show an embodiment of a lead placed such that the longitudinal axis of the lead is aligned (e.g., parallel) to the superficial muscle, but is not aligned (e.g., orthogonal) to the deep muscle, the resulting forces of the muscles acting on the lead, and months of treatment to fracture;

[0134] FIGs. 11H-J show an embodiment of a lead placed such that the longitudinal axis of the lead is aligned (e.g., parallel) to the deep muscle, but is not aligned (e.g., orthogonal) to the superficial muscle, the resulting forces of the muscles acting on the lead, and months of treatment to fracture;

[0135] FIG. 12 shows several examples A-F of lead placement and to identify an approach that aligns with the majority of muscle force and movement with the axis of elasticity of the lead;

[0136] FIGs. 13A-G show anteroposterior and lateromedial views of the examples of lead placement of FIG. 12 and ranges of angles for stimulating lead insertion taking into consideration bony structures of the spine, not including soft tissues (e.g., muscle, fat, connective tissue, etc.);

[0137] FIGs. 14A-C show an embodiment of orienting a lead such that the longitudinal axis of the lead is parallel or mostly parallel with the orientation of the muscles that the lead intersects and the resulting lead shape at rest and during muscle change;

[0138] FIGs. 14D-F show an embodiment of partial alignment of a lead with the orientation of the muscles that the lead intersects increases shear forces at the boundaries of the muscle bundles and the resulting lead shape at rest and during muscle change;

[0139] FIG. 14H-J show an embodiment of placing the lead with the orientation that is orthogonal to the orientation of the muscles that the lead intersects maximizes or further increases shear forces at the boundaries of the muscle bundles and the resulting lead shape at rest and during muscle change;

[0140] FIGs. 15A-D show several embodiments of lead trajectories with respect to muscle bundle orientation (e.g., fascicles) when inserted for placement to target a nerve with electrical stimulation;

[0141] FIGs. 16A-D shows the magnitude of fracture-causing forces from muscle acting on a lead for several embodiments of lead orientation within muscle corresponding to FIGs. 15A-D;

[0142] FIGs. 17A-C shows an embodiment of a method of lead placement including determining the muscle line of action and / or net force and / or net movement of the muscles that the lead will intersect, inserting a lead assembly such that the orientation of the lead assembly is aligned with the orientation of the muscle line of action and / or net force and / or net movement of the muscles that the lead will intersect, and deploying a lead of the lead assembly;

[0143] FIGs. 18A-D show an embodiment of a lead with the longitudinal axis of the lead aligned (i.e., parallel or mostly parallel or within 30 degrees of parallel) with the orientation of muscle bundles (e.g., muscles, muscle planes, muscle fascicles, muscle fibers) under different muscle movements;

[0144] FIGs. 18E-H show an embodiment of a lead with the longitudinal axis of the lead not aligned (e.g., mostly or partially orthogonal or perpendicular) with the orientation of muscle bundles (e.g., muscles, muscle planes, muscle fascicles, muscle fibers) under different muscle movements;

[0145] FIGs. 19A-D show an embodiment of a lead with the longitudinal axis of the lead aligned (i.e., parallel or mostly parallel or within 30 degrees of parallel) with the orientation of muscle bundles (e.g., muscles, muscle planes, muscle fascicles, muscle fibers) under different muscle movements;

[0146] FIGs. 19E-H show an embodiment of a lead with the longitudinal axis of the lead not aligned (e.g., mostly or partially orthogonal or perpendicular) with the orientation of muscle bundles (e.g., muscles, muscle planes, muscle fascicles, muscle fibers) under different muscle movements;

[0147] FIG. 20A is a schematic anatomic view of the lumbar spine in the anterior- posterior view, with paraspinal muscle (e.g., multifidi) bundles (e.g., muscles, muscle fascicles, muscle fibers, muscle planes);

[0148] FIG. 20B illustrates an embodiment of a lead inserted into the body in accordance with carious disclosed aspects herein;

[0149] FIG. 20C shows the lead of FIG. 20B when the surrounding muscle(s) are at rest in accordance with various disclosed aspects herein;

[0150] FIG. 20D shows the lead of FIG. 20B when the surrounding muscle(s) are in contraction in accordance with various disclosed aspects herein;

[0151] FIG. 20E shows the lead of FIG. 20B when the surrounding muscle(s) are elongated in accordance with various disclosed aspects herein;

[0152] FIG. 20F shows an embodiment of a lead inserted into the body in accordance with various disclosed aspects herein;

[0153] FIG. 20G shows the lead of FIG. 20F when the surrounding muscle(s) are at rest in accordance with various disclosed aspects herein;

[0154] FIG. 20H shows the lead of FIG. 20F when the surrounding muscle(s) are in contraction in accordance with various disclosed aspects herein;

[0155] FIG. 201 shows the lead of FIG. 20F when the surrounding muscle(s) are elongated in accordance with various disclosed aspects herein;

[0156] FIG. 20J shows an embodiment of a lead inserted into the body in accordance with various disclosed aspects herein;

[0157] FIG. 20K shows the lead of FIG. 20J when the surrounding muscle(s) are at rest in accordance with various disclosed aspects herein;

[0158] FIG. 20L shows the lead of FIG. 20J when the surrounding muscle(s) are in contraction in accordance with various disclosed aspects herein;

[0159] FIG. 20M shows the lead of FIG. 20J when the surrounding muscle(s) are elongated in accordance with various disclosed aspects herein;

[0160] FIG. 21 shows an embodiment of a lead targeting the lumbar medial branch oriented such that the angle of the lead is primarily parallel with the net forces and / or net movement of the paraspinal muscles (e.g., multifidi);

[0161] FIGs. 22A-C show several embodiments for lead placement on a body having various considerations for insertion and healing;

[0162] FIGs. 23A-C show several embodiments for lead placement on a body having various considerations for insertion and healing;

[0163] FIG. 24 shows a non-exhaustive chart of considerations for the optimization of lead orientation that may be implemented or assessed manually, e.g., by a physician or that may be implemented through computer instructions or artificial intelligence analysis;

[0164] FIG. 25 shows an exemplary execution of the non-exhaustive chart of considerations used in FIG. 24 and a recommended output based on a region of the body;

[0165] FIG. 26A-C show, respectively, anterior-posterior view, oblique view, and lateral views of a needle introducer of a percutaneous lead targeting the lumbar medial branch nerves for the treatment of low back pain and considerations for positions of insertion;

[0166] FIG. 27A-F show data relating to the rate of treatment interruption for existing and strengthened leads and positioning of the leads relative the muscle orientation;

[0167] FIGs. 28A-Q illustrate non-limiting embodiments of stimulating leads for use with the present system and methods;

[0168] FIGs. 29 A illustrate non-limiting embodiments of a curved introducer needle for a percutaneous lead placement in various positions on the spine;

[0169] FIG. 30A shows an embodiment of a needle, lead, and / or electrode for insertion to a target stimulation site with a fixed length;

[0170] FIGs. 30B-C show positioning of the lead in FIG. 30A having a fixed length and inserted toward the target stimulation site having different angles relative the muscle orientation;

[0171] FIGs. 31 A-I illustrate non-limiting embodiments of lead trajectories to stimulate peripheral nerves for the treatment of pain in and around the spine;

[0172] FIG. 32 shows an embodiment of a lead insertion angle for cervical lead placement;

[0173] FIGs. 33A-D show examples of lead placement and the related considerations of aligning the lead with the angle of the muscle bundles, aligning the lead so that it passes through muscles with the least amount of force, and aligning the lead in the direction of muscle net forces for each lead placement and their respective outcome and lead life;

[0174] FIGs. 34A-D show non-exhaustive examples of electrode placement targeting peripheral spinal nerves and expected areas of pain relief;

[0175] FIG. 35 shows non -limiting examples of troubleshooting lead placement.

[0176] FIG. 36A shows an embodiment of placement of a lead to treat pain around the cervical spine, placed in alignment with the primary muscle line of action;

[0177] FIG. 36B-E show exemplary embodiments of placements of a lead to treat pain around the cervical spine, placed in alignment with the primary muscle line of action and / or net vector and in the secondary muscle line of action and / or net vector.

[0178] FIG. 37A-B show exemplary schematics of ultrasound imaging when targeting the lumbar medial branch nerves and placement of a lead based on the imaging;

[0179] FIG. 38 shows data for the fracture rate, migration rate, and lead survival rate for various leads and orientations of the leads;

[0180] FIG. 39A-H show views of the examples of lead placement and angles for stimulating lead insertion taking into consideration anatomical structures.DETAILED DESCRIPTION

[0181] Reference will now be made in detail to exemplary embodiments of the present technology, examples of which are illustrated in the accompanying drawings. It is to be understood that other embodiments may be utilized, and structural and functional changes may be made without departing from the respective scope of the invention. Moreover, features of the various embodiments may be combined or altered without departing from the scope of the invention. As such, the following description is presented by way of illustration only and should not limit in any way the various alternatives and modifications that may be made to the illustrated embodiments and still be within the spirit and scope of the invention. Any elements described herein as singular can be pluralized (i.e., anything described as “one” can be more than one). Any species element of a genus element can have the characteristics or elements of any other species element of that genus. The described configurations, elements or complete assemblies and methods and their elements for carrying out the invention, and variations of aspects of the invention can be combined and modified with each other in any combination. Although the disclosure hereof is detailed and exact to enable those skilled in the art to practice the invention, the physical embodiments herein disclosed merely exemplify the invention, which may be embodied in other specific structures. While the preferred embodiment has been described, the details may be changed without departing from the invention.

[0182] The system, device, method, and instructions for use of systems, devices, and methods discussed below involve inserting a lead into a human body and using electrical stimulation to activate nerve(s) (e.g., peripheral nerve(s)) to provide pain relief. Any method of electrical stimulation will work to activate at least one nerve in the body. In one embodiment, the stimulation system activates peripheral nerves (e.g., peripheral nerves, peripheral spinal nerves, roots, trunks, or branches; FIG. 2A-G) in a way that generates neurally encoded signalsin the afferent fibers, which carry the signals toward the central nervous system, such that the neurally encoded signals modulate central processing of pain.

[0183] The present system, device, method, and instructions for use of systems, devices, and methods are designed to overcome drawbacks of existing neuromodulation technologies, which commonly fail to produce effective pain relief in many cases of spine pain (i.e., pain in or around the spine, pain on the posterior side of the trunk) and / or fail to maintain effective pain relief over time due to mechanical effects on the device from the anatomy near the spine (e.g., forces from muscles). For example, the present invention is designed to overcome drawbacks with TENS (transcutaneous electrical nerve stimulation), which is a non- invasive method to deliver electrical stimulation through surface electrodes to generate paresthesia coverage of the regions of pain. TENS requires perpetual frequent treatment sessions to maintain pain relief, but consistent efficacy has not been demonstrated, while the present invention is designed to provide sustained relief that is long-lasting through the reconditioning of the central nervous system. Although TENS can be self-administered at home, TENS systems can be cumbersome and not practical for daily use due to having to place equipment on the skin in the area of pain for each treatment, while the present invention is designed to be user friendly because the electrodes are placed inside the body by a physician. Also, TENS can activate cutaneous fibers and cause irritation and discomfort, limiting the maximum tolerable stimulation intensity and treatment duration that can be delivered and reducing the potential efficacy of the treatment, while the present invention is designed to avoid the activation of cutaneous fibers by placing the electrodes away from the skin. TENS, while non-invasive, lacks evidence of effectiveness and may produce discomfort from stimulation of cutaneous fibers.

[0184] The present system, device, method, and instructions for use of systems, devices, and methods are also designed to overcome drawbacks of spinal cord stimulation(SCS), which is a method to deliver electrical stimulation through leads implanted in the spinal canal (e.g., in the epidural space) and connected to an implanted pulse generator with a battery and / or an external power source mounted on the skin that delivers of stimulation via the implanted pulse generator. SCS is invasive and commonly associated with device complications that limit successful use by some patients. Spinal cord stimulation requires complex and invasive surgery by highly skilled physicians to implant the leads and pulse generator, while the present invention is designed to require a less invasive placement procedure for the leads and, in an embodiment, an implantable pulse generator. Further, while generation of the desired effect of pain relief with SCS can be difficult, as sensations produced by stimulation are highly dependent on the system programming, electrode placement, and neuroanatomy, which can make application challenging for some pain conditions (e.g., axial pain, pain outside of the limbs, pain not confined to a specific dermatome, etc.), in an embodiment, the invention is designed to achieve sensations robustly and in a manner less dependent on programming and precise placement by delivering electrical stimulation to directly activate the peripheral nerves innervating the region of pain. SCS also has a moderate rate of complications, including additional pain and hardware complications, and as a result, revision surgery, reprogramming, or removal of the stimulator is often required. The present invention is designed overcome the risks of complications associated with SCS. As an example, the present invention enables effective use of a lead(s) that is designed to be flexible and may be coiled lead and otherwise configured to provide an excellent safety profile (e.g., low risk of infection, minimal pistoning or movement in or out of the skin, and enables tissue ingrowth to reduce risk of fracture and dislodgement).

[0185] In recent years, applications of implanted neurostimulation (e.g., spinal cord stimulation) have evolved to include stimulation of the dorsal root ganglion (DRG) for the treatment of chronic neuropathic pain. The DRG describes the collection of peripheral nervecell bodies outside of the epidural space in the spine. DRG systems are implanted using methods similar to SCS (e.g., with an approach through or near the epidural space for thoracic and lumbar targets and a transforaminal approach for sacral targets), however leads and electrodes are moved or placed in proximity to the to the DRG, rather than the spinal cord. This approach is done to provide stimulation therapy to a specific area of the body that does not change with position or movement, which is challenging with typical SCS lead placement. However, DRG systems remain extremely invasive (e.g., require surgery and surgical implant of a pulse generator), require increased time, and are technically challenging to implant; as leads are typically guided through the epidural space and proper placement near the DRG may vary, resulting in recruitment of off-target neural structures (e.g., motor fibers, nerves and cells in the spinal cord) to generate undesirable (e.g., uncomfortable, painful) effects of stimulation.

[0186] Whereas other conventional treatments for pain (e.g., chronic, sub-acute, or acute pain) are often ineffective because they seek only to treat the symptoms and cannot treat the underlying pain condition or central sensitization responsible for pain, the present invention is designed to address the central sensitization by activating the afferent fibers in the peripheral nerves innervating the region of pain. Further, most are not well tolerated and / or associated with side effects and complications. Analgesic medications are commonly used (e.g., acetaminophen, NSAIDs, muscle relaxants, tricyclic antidepressants, corticosteroids) to provide short-term pain relief, but can produce undesirable side effects (e.g., sedation, gastrointestinal problems), while PNS avoids such undesirable side effects by acting directly only on the area nearby / close to / surrounding the leads and indirectly in the central nervous system. Although analgesics can provide substantial pain relief in some, a large proportion of patients do not experience sufficient pain relief. Further, long-term use of medications (e.g., opioids) is not recommended (e.g., to prevent opioid dependence). The present peripheral nerve stimulation system, device, method, and instructions for use of systems, devices, and methodsprovides sustained long-term pain relief without the use of analgesic medications, avoiding the side effects, complications, and risks of abuse, misuse, and dependence that can come from analgesic medications.

[0187] Other approaches to treat pain in the area of the spine include injections of steroids or anesthetics or neuroablation (e.g., radiofrequency, cryoablation), which may provide short-term pain relief (e.g., on the order of a few months), but usually require frequent re-treatment sessions and are associated with side effects and complications (e.g., increased pain, lightheadedness, headache, infection, and nausea and vomiting). Intrathecal drug delivery can be effective for reducing pain, but it requires an invasive procedure and long-term implant and is limited by frequent side effects and technical complications that may require reoperation or removal of the device. Alternative therapies, such as exercise, yoga, or strength training can be effective for certain types of pain, but patients often fail to comply with treatment regimens, so pain returns over time.

[0188] The present system, device, method, and instructions for use of systems, devices, and methods may address the underlying source of dysfunction that is responsible for spine pain or pain in or around the back side of the body (e.g., cervical spine pain, chronic neck pain, lumbar pain, chronic low back pain, sacroiliac joint pain, sacral pain, thoracic pain, chronic mid back pain, chronic high back pain). One of the goals of the invention is to treat or reverse the occurrence of pain without requiring repair and / or treatment of the initiating cause of spine pain (e.g., mechanical injury, structural deformity, or disease). Furthermore, this system provides an effective method to treat spine pain that can avoid the use of multiple, separate therapies, which individually target the original injury or cause of pain and / or fail to correct the central problem of pain processing. In an embodiment, modulation of central pain processing is activated through stimulation of peripheral nerve fibers in the periphery (i.e., outside of the spinal cord), which in turn directly produce afferent neural signals and / or mayalso produce efferent signals that cause activation of paraspinal muscles to indirectly produce afferent neural signals. In an embodiment, the present system allows for treatment of spine pain by altering the central neural nociceptive processing as a result of stimulation of peripheral nerves, preventing pain perception and / or sensation. Unlike other therapies and prior art (e.g., physical therapy, TENS, spinal manipulation, and prior methods of neuromuscular stimulation), which attempt to target (e.g., block or modify) the original source of painful signals (e.g., restoring stability to unstable structures, regions, muscles, and / or components of the neck, strengthening weakened structures, regions, muscles, and / or components of the neck), this method enables directed treatment of the present source of the pain (e.g., the central processing of neural inputs, which can affect the modulation, processing, and / or perception of pain). This invention avoids unintentional discomfort and / or exacerbation of pain that can arise from alternative treatments and prior art targeting peripheral structures (e.g., TENS, physical therapy, and other forms of stimulation). Furthermore, in one embodiment, this system enables pain relief resulting from various (e.g., multiple different) initiating causes of pain, via activation of peripheral nerves and paraspinal muscles and modulation of central pain processing.

[0189] Because the present invention (e.g., including the system(s), device(s), method(s), and methods of using and / or delivering the system, devices, and / or method(s)) can deliver stimulation, generate muscle contractions that are comfortable, and avoid causing discomfort, the present invention can avoid (e.g., preclude, obviate, and / or reduce) the need to provide additional analgesic methods (e.g., pharmaceuticals, additional stimulation) to relieve discomfort caused by the therapeutic stimulation and / or muscle contractions (e.g., the present system and method may be effective and avoid causing discomfort concurrently). In an embodiment, the present system provides a clinically meaningful advantage over previous methods of treating pain (e.g. spine pain and / or other pain) that required methods to relieve theiatrogenic discomfort or pain that could accompany the therapy (e.g., stimulation-evoked discomfort and / or muscle contractions that caused discomfort). In a non-limiting example embodiment, because the present system, device, method, and instructions for use of systems, devices, and methods do not require (e.g., avoids and / or avoids the need for) stimulation of muscles at a level (e.g., intensity, frequency, duration, and / or other parameter setting) necessary to cause functional changes, such as strengthening, stability, which may require uncomfortable muscle contractions, the present system may avoid delivering painful stimulation and / or avoids other painful responses, such as painful or uncomfortable muscle contractions, and delivers non-painful stimulation that comfortably contracts and / or relaxes muscle in a way that generates neurally encoded signals in afferent nerve fibers that modulate central pain processing, reducing the sensation and / or perception of pain. Furthermore, in an embodiment, the pain relief produced by the invention outlasts the duration of stimulation provided by the invention due to the modulation or resetting of the central pain processing center(s), enabling a temporary system to be used to provide long term relief of spine pain. In another embodiment, the pain relief produced by the invention outlasts the duration of stimulation provided by the invention, enabling lower power consumption (e.g., power consumption from an external and / or implantable battery, or fewer recharge-cycles of the external and / or implanted battery), reducing the need for the patient to use the device as much, as regularly, or continuously, and / or reducing the reliance of effective pain relief on patient compliance with device usage. In another embodiment, the pain relief produced by the invention may not outlast the duration of stimulation provided by the invention (e.g., the pain relief may last for less than, equal to, or more than the duration of stimulation).

[0190] In an embodiment, the present system, device, method, and instructions for use of systems, devices, and methods, in addition to reducing the perception of pain immediately or while stimulation is on, modulates central neural processing (e.g., in the CNS, such as the spinalcord, brain, and / or other central neural processing centers) to reduce the perception of pain long-term (e.g., for many months, for many years, permanently), and this modulation of central neural processing is achieved without requiring blocking of transmission of pain signals from periphery (e.g., through peripheral and / or spinal nerves and distal branches) to the central nervous system. As a non-limiting example, the therapy makes use of existing natural processes of neural signal encoding by muscles, evoked through nerve stimulation, which can modulate pain processing, without use of and avoiding signal transmission blockade (e.g., by neuroablative procedures or surgery, which permanently damage nerves and seek to block transmission of signals to central processing centers, or by electrical stimulation). As a nonlimiting example, the system and method modulates central neural processing (e.g., in the CNS such as the spinal cord, brain, and / or other central neural processing centers) to reduce the perception of pain long-term (e.g., for many months, for many years, permanently), and this modulation of central neural processing is achieved without requiring stimulation-evoked motor contractions or patient-reported sensations (e.g., sub-perception) arising from stimulation. In an embodiment, the system directly addresses the manifestation of pain at the central neural processing level, unlike other systems, which focus on modifying or blocking incoming signals from the periphery (i.e., failing to address cause of pain).

[0191] In an embodiment, the present system, device, method, and instructions for use of systems, devices, and methods modulate central neural processing (e.g., in the CNS, such as the spinal cord, brain, and / or other central neural processing centers) to reduce the perception of pain, and this modulation of central neural processing is achieved without requiring blocking of transmission of neural (e.g., nerve or nerve fiber) signals from periphery (e.g., through peripheral and / or spinal nerves and distal branches) to and / or from the central nervous system. In an embodiment, the present system and method modulates central neural processing without nerve blocking because the invention enables reduction and / or elimination of pain viamodulation of central neural processing (i.e., nerve block is not required, and the present invention desirably avoids nerve block).

[0192] The present invention overcomes certain limitations of the prior art by describing systems, devices, and methods that teach the optimal way(s) to insert, place, or implant a lead in a human body to increase the potential for durable pain relief, while avoiding forces from the surrounding musculature that may interrupt treatment by causing the lead to fracture and / or migrate from the original position of the lead.

[0193] In the human body, 31 pairs of peripheral nerves derive from the spinal cord such that one bilateral pair of nerves (a left and right nerve) exits the spinal cord per spinal segmental level of the vertebral column and exist in the periphery, wherein the nerves are named and grouped by spinal region from which they branch or derive, but are peripheral nerves. Peripheral nerves, including these peripheral nerves that derive from the spinal cord and are sometimes called “spinal nerves”, are outside of the spinal cord and not part of the central nervous system. Peripheral nerves are part of the periphery and part of the peripheral nervous system. These nerves are composed of both sensory and motor peripheral nerve fibers that play an important role and serve to communicate information from the periphery to the central nervous system (i.e., brain, spinal cord). These peripheral nerves are mixed nerves that transmit sensory, motor, and / or autonomic impulses between (e.g., to and / or from) the spinal cord and the rest of the body.

[0194] While it was previously believed that the application of electrical stimulation achieved its results by strengthening muscles through repetitive and robust muscle contractions (e.g., contractions so intense that patients with other methods and systems were required to stop other activities and lie flat on the back and / or motionless during therapy, or stimulation was anticipated to be delivered at a level that would cause pain and / or discomfort and / or fatigue), recent investigation has shown that more effective pain relief can be achieved throughstimulation with the method and system in a manner that maximizes relief and minimizes fatigue (e.g., contractions are noticeable but comfortable and / or are strong enough to produce comfortable sensations in the region of pain but not too strong such that patients are able to utilize the muscles being stimulated and otherwise complete normal daily activities without discomfort) and improves device performance, enabling durable pain relief while avoiding adverse events (e.g., pain, discomfort, muscle spasms which may result from overstimulation) and avoids technical complications such as lead migration, lead fracture, lead dislodgement, and / or loss of stimulation efficacy or pain relief. For example, the present system, device, method, and instructions for use of systems, devices, and methods deliver stimulation that is more comfortable and more tolerable for a longer period of time (e.g., 6-12 hours per day in one embodiment) and avoids the need to break stimulation therapy into shorter sessions for patient tolerability (e.g., use of 30 minute sessions 1-2 times per day to prevent patient discomfort), thus increasing the amount of therapeutic stimulation delivery that can provide more robust and durable improvements in pain compared to shorter therapy sessions with the prior art. For example, a non-limiting example of spine pain etiology treated with the present system and method includes or coincides with mechanical issues, issues with muscle weakness, reduced stability, instability, atrophy, hypertrophy, or other conditions and diseases. The present system is designed to modulate the central nervous system such that pain is eliminated or reduced, regardless of the underlying spine pain etiology. In an embodiment, the present invention (e.g., including the system(s), device(s), method(s), and methods of using and / or delivering the system, devices, and / or method(s))treats pain with or without the presence of a specific disease, condition, etiology, imaging finding(s), and / or result(s) of one or more diagnostic examinations or physical tests.

[0195] In the human body, the musculoskeletal system, including the vertebrae, other bones, muscles, tendons, ligaments, soft tissues, vertebral disks, joints, and other structures ofthe spine, interact to support the body and engage in movement. The present system and method are designed to interact with the musculoskeletal system (e.g., enable placement of the lead(s) and electrode(s) that avoid or circumvent bones and avoid or limit shear forces acting on the lead and electrodes from and around muscles) while avoiding complications such as lead dislodgement, lead migration, and / or lead fracture, and / or loss of stimulation efficacy or pain relief. In addition to nerve selection (e.g., targeting a specific nerve to provide pain relief for a specific pain etiology), parameter adjustment (e.g., selecting a waveform frequency, amplitude, and pulse duration to evoke a desired neural response), and electrode location (e.g., for selective activation of a target nerve and / or selective activation of target fibers in the nerve), considerations for the interaction between complex musculoskeletal dynamics and the stimulation system (e.g., electrode, lead, and / or pulse generator) must be made in order to maximize the effectiveness of the peripheral nerve stimulation system (e.g., pain relief) and minimize the potential for treatment interruptions (e.g., lead dislodgement, lead migration, and / or lead fracture).

[0196] During activities of daily living, such as but not limited to ambulating, feeding, dressing, addressing personal hygiene (e.g., brushing teeth, showering), and toileting, muscles of the spine, including but not limited to paraspinal muscles, contract and produce force by bulging, shortening, lengthening, or maintaining length. Additionally, when a muscle pulls on a connective tissue (e.g., tendons, aponeuroses), elastic energy is stored and returned during movement. Together, the force-generating capacity of a single muscle-tendon unit can have significant impact on the integrity of an implanted device. Activities throughout the day create combinations of different muscle groups eliciting varying types, levels, magnitudes, and / or intensities of forces. As such, any lead or electrode that passes through one or more muscles of or near the spine would experience some combination of tensile forces, compressive forces, shear forces, and / or bending forces at one or more locations along the lead or electrode. Whileprevious systems and methods have sought to strengthen the lead (e.g., increasing the tensile, shear, bending, or other measure of strength or durability) to mitigate the effects of forces applied on the lead by the tissues surrounding the lead, these mechanical changes to the lead without consideration of the orientation of the lead, method of insertion, and design of the mechanical properties in the context of the force environment in the dynamic musculoskeletal system have been insufficient to prevent complications such as lead fracture, migration, or dislodgement, and the present system, device, method, and instructions for use of systems, devices, and methods maximize the effectiveness of the system (e.g., pain relief) while avoiding treatment interruptions (e.g., lead dislodgement, lead migration, and / or lead fracture) by requiring orienting, placing, and / or positioning the lead and / or electrode in a way that minimizes negative effects (e.g., tensile forces, compressive forces, shear forces, and / or bending forces) from the muscles and surrounding structures through which the lead and / or electrode pass. It is to be appreciated that optimizing the orientation of the lead and / or electrode relative to the surrounding structures requires understanding of the musculoskeletal anatomy and its corresponding dynamics, and that simply aligning the lead and / or electrode with the apparent direction of the muscle (e.g., from insertion to insertion) may not optimally align the lead and / or electrode with the apparent direction of the deleterious effects (e.g., tensile forces, compressive forces, shear forces, and / or bending forces) because of the complex and highly dynamic nature of the musculoskeletal system. It is also to be appreciated that optimizing the orientation of the lead relative to the surrounding tissue structures may conflict with a number of other factors that impact the success of lead insertion and therapeutic stimulation delivery, such as target electrode location and orientation, lead insertion point (also called lead exit site) at the skin, and the path through the tissue and tissue boundaries. As discussed below, examples of musculoskeletal dynamics that may influence forces acting on the lead and / or electrode include, but are not limited to, muscle lengthening, muscle constricting, muscle bulging,muscle shortening, muscle twisting, muscle change in angle, muscle rotation, muscle structure, muscle gearing, and the interaction between muscles and other muscles or other surrounding structures (FIG. 3). It is to be appreciated that muscle contractions that impact the success of lead insertion and therapeutic stimulation delivery may result from normally occurring bodily movements (e.g., postural contractions of muscles that stabilize the spine, contractions of muscles for normal body movements associated with activities of daily living), direct or indirect activation by electrical stimulation (e.g., contractions which are directly or indirectly caused by electrical stimulation), or changes in muscle contractions as a result of functional improvements following pain relief (e.g., increased frequency or strength of muscle activity due to behavior or health changes as a result of stimulation treatment). Therefore, the present invention is designed to enable lead placement to withstand these forces, ensuring successful therapeutic delivery of stimulation even in the presence of these contractions, which could otherwise impact successful delivery of the prescribed therapeutic stimulation treatment.

[0197] One of the most basic units of a muscle is a myofibril, a bundle of proteins that contain the contractile filaments that produce force. A bundle of myofibrils forms a muscle fiber, otherwise known as a muscle cell (FIG. 4). A bundle of muscle fibers forms a muscle fascicle and is surrounded by connective tissue called perimysium. Together, bundles of muscle fascicles form skeletal muscle and produce aggregate muscle force. During a contraction, a muscle may remain isometric (i.e., no or minimal change in length), may shorten or lengthen in the longitudinal direction, and / or may shorten or lengthen in the transverse direction (e.g., bulging). As such, any lead or electrode that passes through one or more muscles of / near / surrounding / supporting the spine would experience some combination forces and / or movement at one or more locations along the lead or electrode. As an example, the present invention teaches that lead placement with one or more electrodes placed in the midbelly (i.e., thickest portion) of the muscle and / or avoiding placement near the boundary of the muscleminimizes the impact of muscle forces and / or movement that would displace or move the lead and / or electrode away from the target location, thus maintaining a desired therapeutic distance away from the nerve (e.g., avoiding or reducing the impact on the lead or electrode location of muscle bulging or other movements that would otherwise momentarily or permanently displace the electrode away from the nerve) and avoiding migration and dislodgment of the lead and / or electrode.

[0198] Relative to the longitudinal direction of the entire muscle (e.g., the line, direction, vector, or plane from muscle origin to muscle insertion), muscle fascicles are oriented at an angle (i.e., pennation angle) to provide a mechanical advantage and increase the amount of force generating elements in the same cross-sectional area. As shown in FIG. 5, muscles can vary in the arrangement of fascicles. As an example, muscles may have parallel muscle fascicles (FIG. 5 A), wherein a series of muscle fascicles run parallel to the longitudinal axis of the muscle, and / or muscles may have unipennate muscle fascicles (FIG. 5B), wherein the muscle fascicles are arranged at an angle and insert on one side of a tendon, and / or muscles may have bipennate fascicles (FIG. 5C), wherein the muscle fascicles are arranged at an angle and insert on opposite sides of a central tendon, and / or muscles may have multipennate muscle fascicles (FIG. 5D), wherein the muscle fascicles are arranged at an angle on multiple tendons that taper towards a common tendon. As non-limiting examples, the rectus abdominis has parallel fascicles, the flexor pollicis longus has unipennate fascicles, the rectus femoris has bipennate fascicles, and the deltoid as multipennate fascicles. It is appreciated that muscles may be homogenous (with most or all fascicles arranged in the same orientation), heterogenous (with fascicles varying in orientation), and / or have some combination of pennate and / or non- pennate muscle fascicles, and / or may be arranged in another manor or kind (non-limiting examples include fusiform muscles with expanded muscle bellies, convergent muscles with extended fascicles that have a common point of attachment, or circular muscles with fasciclesarranged as concentric rings, etc.). Muscles can vary in the degree of pennation angle of fascicles, for example, most multifidus muscle fascicles (paraspinal muscle) have pennation angles around 10 degrees at rest while most soleus muscle fascicles have pennation angles around 30 degrees at rest. It is appreciated that the muscle bundle (e.g., muscle plane, muscle fascicle, muscle fiber) axis of length change may be the same as the entire muscle’s axis of length change, or it may be an angle relative to the entire muscle’s axis of length change, or it may be at varying angles relative to the entire muscle’s axis of length change (FIG. 6).

[0199] Muscle force and / or muscle shape change is the result of a muscle fascicle changing length and / or rotating (e.g., changing pennation angle). As an example, during most muscle contractions that involve longitudinal muscle shorting and transverse muscle lengthening (i.e., bulging), the action of the entire muscle is the result of fascicles shortening (i.e., decreasing in length) and rotating (i.e., increasing in pennation angle). It is to be appreciated that a muscle can shorten in the longitudinal direction by only decreasing in fascicle length or by only increasing in fascicle pennation angle. However, for mechanically diverse functions, length and pennation angle each contribute and combine to maximize effectiveness (e.g., meeting the demands for force or velocity) by engaging in muscle gearing. As a result of these mechanically diverse functions and the contributions of both length and pennation angle changes, a lead and / or electrode passing through or placed in one or more muscles is likely to or has the potential to experience forces in one or more different axes, directions, planes, or vectors, and these forces can cause movement or stress on the lead and / or electrode, which could limit the therapeutic delivery of stimulation by interrupting treatment. Muscle gearing is the dynamic interplay between force, velocity, and power during a muscle contraction, and through changes in pennation angle and length, muscle gearing enables a muscle to facilitate velocity output during low-load contractions and force output during high- load contractions. However, any changes in muscle gearing, facilitated via changes inpennation angle and length (e.g., fascicle length or longitudinal muscle length or transverse muscle length), increase forces (e.g., shear forces and bending forces) on leads and / or electrodes that pass through or come in contact with muscle.

[0200] Generally, disclosed are systems and methods 100 for inserting a lead 50 including one or more electrodes 53 into a region of the body 5, muscle or muscle bundle 20, and / or target area 7 of stimulation thereof, to provide electrical stimulation to a target nerve 10. The disclosed systems and methods 100 may provide, in an example, pain relief or any other physiological outcomes as may be desired. The disclosed systems and methods 100 may be used and applied to any target nerve 10 and muscle or muscle bundle 20 in the body. The disclosed systems and methods 100 may be executed or determined manually, for example by a physician, or may be generated by a computer readable program or artificial intelligence (or machine learning). The disclosed systems and methods 100 may be customized to a particular target nerve 10 and muscle or muscle bundle 20 and / or may be customized to a particular morphology or anatomy of a patient, e.g., through imaging.

[0201] Reference herein may be made to the orientation, angle, acting force, and the like 32 related to muscle bundle, muscles, and the like 20. It is noted that the orientation or acting force 32 of the muscle 20 may determine, in whole or in part, the placement of the lead 50 in the disclosed systems and methods. Reference herein may be made to the longitudinal axis 56 of the lead 50, which may refer to the axis of the body of the lead 50, in an embodiment. As described herein, the longitudinal axis 56 of the lead 50 may be aligned with the orientation or acting force 32 of the muscle 20 (or one or more muscles, 20, 20’) to minimize force acting on the lead 50. Lead 50 may be inserted into a body region at an angle relative the muscle 20 or bone, e.g., angle 62 of lead 50. Lead 50 may be inserted into a body region at an angle relative the skin , e.g., angle 64 of lead 50.

[0202] The disclosed systems and methods 100 may be used with any lead 50 (even if a particular lead is illustrated and described in the figures), including coiled leads, non-coiled leads, leads with implantable pulse generators, leads with external pulse generators, leads with improved strength or flexibility, leads with a variable number of electrodes, leads with variable anchor shapes and a variable number of anchors, conventional leads, and the like.

[0203] Often a lead 50, inserted into the region of the body or muscle 20 and into the target area 7 of stimulation, may be placed generally perpendicular or orthogonal to the body 5. Leads 50, including permanent leads, non-permanent leads, implantable leads, leads attached to an external stimulator, etc., in this perpendicular or orthogonal position may be prone to fracture, migration, and / or displacement due to muscle forces applied to the lead and normal body movement. It is noted that forces as herein described may refer to as normalized forces or may include forces measured in N or kg m / s2. The fracture, migration, and / or displacement can irreversibly change shape of the lead 50, move the lead 50 out of the target area 7 of stimulation, and / or otherwise prevent or inhibit electrical stimulation to the nerve making the treatment less effective or non-effective. Shortening of lead 50 life may also result in additional needed surgeries or procedures to replace or reposition the leads 50, which can lead 50 to complications, additional healing, and increased costs, for example.

[0204] The disclosed systems and methods 100, however, can provide improved lead 50 life, minimize forces applied to the lead 50 during use, lower the risk and incidence of lead 50 fracture, migration, and / or displacement, facilitate lead movement to generally correspond with muscle movement, and / or otherwise allow consistent treatment and placement of the lead overtime. Generally, the disclosed systems and methods 100 may comprise inserting or placing the lead 50 in a position that is generally parallel or aligned with the orientation 32 of the corresponding muscle or muscle bundle 20. For example and as shown in FIG. 4 insertion of the lead 50 may be parallel to or align with the muscle 20, muscle fascicles 22, muscle fibers24, and / or the myofibrils 26. It is noted herein that the term muscle 20 and muscle orientation 32 may be interchangeable with the terms muscle bundle, muscle fascicles, muscle fibers, myofibrils, muscle planes, muscle line of action, the orientations of any of the preceding, and the like unless context or this disclosure suggests otherwise. It is noted that described angles relative the body and described angles relative the orientation of the muscles 20 may be in relation to a longitudinal axis of the lead 50.

[0205] In an embodiment, the disclosed systems and methods 100 may comprise inserting or placing the lead 50 in a position that is parallel or aligned with the orientation 32 of the corresponding muscle or muscle bundle 20, in a position that is + / - 5° from parallel or alignment with the orientation of the muscle or muscle bundle 20, in a position that is + / - 10° from parallel or alignment with the orientation of the muscle or muscle bundle 20, in a position that is + / - 15° from parallel or alignment with the orientation of the muscle or muscle bundle 20, in a position that is + / - 20° from parallel or alignment with the orientation of the muscle or muscle bundle 20, in a position that is + / - 25° from parallel or alignment with the orientation of the muscle or muscle bundle 20, in a position that is + / - 30° from parallel or alignment with the orientation of the muscle or muscle bundle 20, in a position that is + / - 35° from parallel or alignment with the orientation of the muscle or muscle bundle 20, in a position that is + / - 40° from parallel or alignment with the orientation of the muscle or muscle bundle 20, in a position that is + / - 45° from parallel or alignment with the orientation of the muscle or muscle bundle 20.

[0206] It is noted that any disclosed values or value ranges described herein may include a + / - of 2°. It is noted that parallel or aligned may generally refer to a range of + / - 45° from parallel or alignment with the orientation of the muscle or muscle bundle 20 or may generally refer to any of the ranges described herein (e.g., exactly parallel or aligned to + / - 5° to + / - 45° and any values therebetween) unless context or this disclosure suggests otherwise.

[0207] Turning to FIG. 1 A, shown is a schematic anatomic view of the lumbar spine in the anterior-posterior view, with paraspinal muscle (e.g., multifidi) bundles 20 (e.g., muscles, muscle fascicles, muscle fibers, muscle planes) primarily starting cephalad and terminating caudad. The lumbar medial branch of the dorsal ramus nerve or target nerve 10 may originate near the superior articular process and run between the superior articular process and the transverse process of the vertebral body caudad.

[0208] FIG. IB shows an embodiment of a lead 50 including one or more electrodes 53 inserted into the lumbar spine region of the body 5 to stimulate the target nerve 10. In an embodiment, lead 50 and position of lead 50 may be generally aligned with the muscle bundle 20 (e.g., the muscle line of action). In an embodiment, lead 50 and position of lead 50 prevent interruption of therapeutic delivery causes by lead fracture, migration, and / or displacement reversibly changing lead-shape in response to forces applied on the lead 50.

[0209] Here, as shown in FIG. 1C, an open-coiled lead 50 may be percutaneously placed such that the longitudinal axis of the lead, with initial shape LLI, is primarily aligned with muscle bundles 20 at rest (LMI). AS shown in FIG. ID, during muscle contraction or musculoskeletal compression (LM2), the lead 50 avoids fracture, migration, and / or displacement by changing shape (LL2). AS shown in FIG. IE, during muscle elongation or musculoskeletal tension (LM3), the lead 50 avoids fracture, migration, and / or displacement by changing shape (LL3). In a preferred embodiment, lead 50 shape changes are intentional, reversible, and reservable.

[0210] FIGs. 2A and 2B are schematic anatomic views, respectively anterior and lateral, of a human peripheral nervous system. FIG. 2C is a schematic anatomic view of a human spine, showing the various regions and the vertebrae comprising the regions. FIGs. 2D and 2E are schematic anatomic views of the dermatome boundaries of a human. FIGs. 2F and2G are anatomic views of the intercostal spinal nerves of a human. The disclosed systems and methods 100 may be used with any of the region of the body 5 shown in FIGs. 2A-G.

[0211] As described herein, the disclosed systems and methods 100 may comprise orienting a lead 50 generally parallel or in alignment with a corresponding muscle 20 so as to minimize fracture, migration, and / or displacement of the lead 50 as the muscle 20 moves and changes shape, for example. FIG. 3 illustrates a non-exhaustive ways that a muscle or muscle bundle 20 (e.g., muscle fascicle, muscle fiber, muscle plane) can change shape during activities of daily living, during movement, standing, sitting, sleeping, or during stimulation or as a result of stimulation. Starting with an initial longitudinal length (LLo), initial angle (0o), and initial transverse length (TLo), as shown in FIG. 3A, a muscle or muscle bundle 20 (e.g., muscle fascicle, muscle fiber, muscle plan) can lengthen (FIG. 3B; increase in longitudinal length), constrict (FIG. 3C; decrease in transverse length), bulge (FIG. 3D; increase in transverse length), shorten (FIG. 3E; decrease in longitudinal length), twist (FIG. 3F, rotate at one point more than it rotates at another point), and / or change in angle (FIG. 3G).

[0212] As described herein, the disclosed systems and methods 100 may comprise inserting or placing the lead 50 in a position that is generally parallel or aligned with the orientation of the corresponding muscle or muscle bundle 20. For example and as shown in FIG. 4, insertion of the lead 50 may be parallel to or align with the muscle 20, muscle fascicles 22, muscle fibers 24, and / or the myofibrils 26 wherein the muscle may be joined to a tendon and bone. FIG. 4 is a schematic representation of musculoskeletal morphology. One of the most basic units of a muscle is a myofibril, a bundle of proteins that contain the contractile filaments that produce force. A bundle of myofibrils forms a muscle fiber, otherwise known as a muscle cell. A bundle of muscle fibers forms a muscle fascicle and is surrounded by connective tissue called perimysium. Together, bundles of muscle fascicles form skeletal muscle and produce aggregate muscle force. The muscle or muscle bundle 20 may be understood as being orientedin a particular direction or having forces exerted in a particular direction based on the orientation or one or more (or all) its components, including the muscle fascicles 22, muscle fibers 24, and / or the myofibrils 26. Skeletal muscle typically pulls on a connective tissue (e.g., tendons, aponeuroses), which is attached to bone.

[0213] Similarly, FIG. 5 illustrates non-exhaustive arrangements of fascicles 22 within a muscle 20. As non-limiting examples, muscles 20 may have parallel muscle fascicles 22 (FIG. 5 A), wherein a series of muscle fascicles 22 run parallel to the longitudinal axis of the muscle 20, and / or muscles 20 may have unipennate muscle fascicles 22 (FIG. 5B), wherein the muscle fascicles 22 are arranged at an angle and insert on one side of a tendon, and / or muscles 20 may have bipennate fascicles (FIG. 5C), wherein the muscle fascicles 22 are arranged at an angle and insert on opposite sides of a central tendon, and / or muscles 20 may have multipennate muscle fascicles 22 (FIG. 5D), wherein the muscle fascicles 22 are arranged at an angle on multiple tendons that taper towards a common tendon. FIG. 6 illustrates non-exhaustive examples of muscles with fascicles whose axis of longitudinal length change is generally parallel (FIG. 6A) to longitudinal muscle length change or at an angle (0i, FIG. 6B) to longitudinal muscle length change. FIG. 6C illustrates two muscle planes (e.g., a bipennate muscle, two separate muscles), with one plane at an angle 0x and a second plane at an angle 0Y.

[0214] In an embodiment, each of these orientations in FIGs. 5-6 (and others not shown) may exhibit different forces in different directions. The disclosed systems and methods 100 may comprise inserting or placing the lead 50 in a position that is generally parallel or aligned with the orientation, forces, and directions of forces in a muscle 20 so that the lead 50 may move with the muscle 20 and minimize the forces acting on the lead 50, for example.

[0215] As shown in FIG. 7, desired placement of a lead 50 may traverse or extend through more than one muscle or muscle bundle 20. The disclosed systems and methods 100may account for the orientation, forces, and directions of forces in each muscle or muscle bundle 20 and / or may minimize the number of muscles or muscles bundle 20 (e.g., such as those having different orientation, forces, and directions of forces) that are crossed by the lead 50. For example, FIG. 7A shows an embodiment of a lead 50 placed orthogonal (e.g., approximately 90-degree angle) to a longitudinal axis of movement or net force of two muscles, muscle planes, or muscle bundles (e.g., fascicles) 20. As shown in FIG. 7B, during contraction, where one muscle 20 may move, displace, bulge, constrict, contract, or lengthen more than another muscle, muscle plane, or muscle bundle 20, a lead 50 that crosses both muscle planes 20 may undergo shear forces at the muscle boundary conditions that result in lead fracture, migration, displacement, and / or dislodgement, which can interrupt therapeutic stimulation and ability to provide prescribed treatment.

[0216] FIG. 7C, on the other hand, shows an embodiment of a lead 50 that is generally aligned with a longitudinal axis of movement or net force of one or more muscle, muscle plane, or muscle bundle (e.g., fascicles) 20. As shown in FIG. 7D, during a contraction, where one muscle 20 may move, displace, bulge, constrict, contract, or lengthen more that another muscle, muscle plane, or muscle bundle 20, a lead 50 that is placed (e.g., within 30 degrees) parallel to the muscle line of action, direction of muscle movement, or net force avoids lead fracture, migration, displacement and / or dislodgement, thus ensuring therapeutic delivery of stimulation for the entirety of the prescribed treatment period (e.g., days, weeks, months, years).

[0217] In embodiments where the entirety of a lead 50 (e.g., and implantable pulse generator) may not be isolated to a single muscle 20 as in FIG. 7C (e.g., due to placement of the lead 50, location of the target nerve 10, surrounding musculature 20, desired position of entrance into the body, etc.), the disclosed systems and methods 100 may account for the cumulative forces exerted by the more than one muscles 20 to determine which orientation and alignment of the lead 50 relative the more than one muscles will result in the lease amount ofcumulative force or which will otherwise me more desirable. FIGs. 8-11, for example, show various positions of a lead 50 that crosses more than one muscle or muscle bundle 20 having different orientation, forces, and directions of forces in each muscle or muscle bundle 20 and the resulting forces on the lead 50 in these positions.

[0218] For example, FIGs. 8-11 illustrate embodiments of lead 50 placement orientations for a percutaneously placed lead 50 that crosses two muscle bundles 20 (e.g., muscles, muscle planes, muscle fascicles, muscle fibers), labeled 1) superficial muscle and 2) deep muscle. As shown in FIG. 8A, 9A, 10A, and 11 A, the deep muscle may have a larger peak for generating capacity (i.e., amount of forces each muscle can produce that cause lead fracture, dislodgment, or migration) than the superficial muscle, which may have a smaller peak for generating capacity. It is noted that other muscles may have different generating capacities than shown. Generally, disclosed systems and methods 100 may prioritize alignment of the lead 50 with the muscle having the larger peak for generating capacity so as to minimize the cumulative force exerted on the lead 50 by both muscles, see, for example, FIGs. 8B-G, 9B-J, 10B-J, and 11B-J.

[0219] In FIG. 8B, a coiled lead 50 is placed perpendicular to the superficial boundary, and thus is not aligned with either the superficial muscle or the deep muscle. As such, as shown in FIG. 8C, the magnitude of fracture-causing forces acting on the lead 50 has large contributions from the superficial muscle and the deep muscle, thereby surpassing the threshold needed for the lead 50 to fracture, migrate, or dislodge.

[0220] In FIG. 8D, a coiled lead 50 is placed such that the longitudinal axis of the lead50 is aligned (e.g., parallel) to the superficial muscle, but is not aligned (e.g., orthogonal) to the deep muscle. As such, as shown in FIG. 8E, the magnitude of fracture-causing forces acting on the lead 50 has minimal contributions from the superficial muscle but large contributionsfrom the deep muscle (which produces more deleterious forces), thereby surpassing the threshold needed for the lead 50 to fracture, migrate, or dislodge.

[0221] In FIG. 8F, a coiled lead 50 is placed such that the longitudinal axis of the lead 50 is aligned (e.g., parallel) to the deep muscle, but is not aligned (e.g., orthogonal) to the superficial muscle. As such, as shown in FIG. 8G, the magnitude of fracture-causing forces acting on the lead 50 has minimal contributions from the deep muscle and large contributions from the superficial muscle (which has the smaller force generating capacity), thereby avoiding lead 50 fracture, migration, and dislodgment and facilitating continuation of treatment.

[0222] In FIG. 9B, a coiled lead 50 is placed perpendicular to the superficial boundary, and thus is not aligned with either the superficial muscle or the deep muscle but passes through both the superficial and deep muscle. As such, as shown in FIG. 9C, the magnitude of fracturecausing forces acting on the lead 50 has large contributions from the superficial muscle and the deep muscle, thereby surpassing the threshold needed for the lead 50 to fracture, migrate, or dislodge. As shown in FIG. 9D, not aligning the lead 50 with the orientation of net muscle force results in premature treatment interruption.

[0223] In FIG. 9E, a coiled lead 50 is placed such that the longitudinal axis of the lead 50 avoids the superficial muscle, but is placed in the deep muscle, but not aligned (e.g., orthogonal) with the relative orientation of the deep muscle. As such, as shown in FIG. 9F, the magnitude of fracture-causing forces acting on the lead 50 has no contributions from the superficial muscle but large contributions from the deep muscle (which produces more deleterious forces), thereby surpassing the threshold needed for the lead 50 to fracture, migrate, or dislodge. As shown in FIG. 9G, not aligning the lead 50 with the orientation of net muscle force results in premature treatment interruption.

[0224] In FIG. 9H, a coiled lead 50 is placed such that the longitudinal axis of the lead50 is aligned (e.g., parallel) to the deep muscle, and avoids the superficial muscle. As such, asshown in FIG. 91, the magnitude of fracture-causing forces acting on the lead 50 has minimal contributions from the deep muscle and no contributions from the superficial muscle, thereby avoiding lead fracture, migration, and dislodgment and facilitating continuation of treatment as shown in FIG. 9J.

[0225] In FIG. 10B, a coiled lead 50 is placed perpendicular to the superficial boundary, and thus is not aligned with either the superficial muscle or the deep muscle. As such, as shown in FIG. 10C, the magnitude of fracture-causing forces acting on the lead 50 has large contributions from the superficial muscle and the deep muscle, thereby surpassing the threshold needed for the lead 50 to fracture, migrate, or dislodge. As shown in FIG. 10D, not aligning the lead 50 with the orientation of net muscle force results in premature treatment interruption.

[0226] In FIG. 10E, a coiled lead 50 is placed such that the longitudinal axis of the lead 50 is aligned (e.g., parallel) to the superficial muscle, but is not aligned (e.g., orthogonal) to the deep muscle. As such, as shown in FIG. 10F, the magnitude of fracture-causing forces acting on the lead 50 has minimal contributions from the superficial muscle but large contributions from the deep muscle (which produces more deleterious forces), thereby surpassing the threshold needed for the lead 50 to fracture, migrate, or dislodge. As shown in FIG. 10G, not aligning the lead 50 with the orientation of net muscle force results in premature treatment interruption.

[0227] In FIG. 10H, a coiled lead 50 is placed such that the longitudinal axis of the lead 50 is aligned (e.g., parallel) to the deep muscle, but is not aligned (e.g., orthogonal) to the superficial muscle. As such, as shown in FIG. 101, the magnitude of fracture-causing forces acting on the lead 50 has minimal contributions from the deep muscle but minimal contributions from the superficial muscle (which produces less deleterious forces), therebyavoiding lead 50 fracture, migration, and dislodgment and facilitating continuation of treatment as shown in FIG. 10 J.

[0228] In FIG. 11B, a non-coiled lead 50 is placed perpendicular to the superficial boundary, and thus is not aligned with either the superficial muscle or the deep muscle. As such, as shown in FIG. 11C, the magnitude of fracture-causing forces acting on the lead 50 has large contributions from the superficial muscle and the deep muscle, thereby surpassing the threshold needed for the lead 50 to fracture, migrate, or dislodge. As shown in FIG. 1 ID, not aligning the lead 50 with the orientation of net muscle force results in premature treatment interruption that occurs before completion of the prescribed number of cycles.

[0229] In FIG. 1 IE, a non-coiled lead 50 is placed such that the longitudinal axis of the lead 50 is aligned (e.g., parallel) to the superficial muscle, but is not aligned (e.g., orthogonal) to the deep muscle. As such, as shown in FIG. 1 IF, the magnitude of fracture-causing forces acting on the lead 50 has minimal contributions from the superficial muscle but large contributions from the deep muscle (which produces more deleterious forces), thereby surpassing the threshold needed for the lead 50 to fracture, migrate, or dislodge. As shown in FIG. 11G, not aligning the lead 50 with the orientation of net muscle force results in premature treatment interruption that occurs before completion of the prescribed number of cycles.

[0230] In FIG. 11H, a non-coiled lead 50 is placed such that the longitudinal axis of the lead 50 is aligned (e.g., parallel) to the deep muscle, but is not aligned (e.g., orthogonal) to the superficial muscle. As such, as shown in FIG. I ll, the magnitude of fracture-causing forces acting on the lead 50 has minimal contributions from the deep muscle but minimal contributions from the superficial muscle (which produces less deleterious forces), thereby avoiding lead 50 fracture, migration, and dislodgment and facilitating continuation of treatment that allows for completion of the number of prescribed cycles as shown in FIG. 11 J.

[0231] FIG. 12 shows several examples A-F of lead placement and to identify an approach that aligns with the majority of muscle force and movement with the axis of elasticity of the lead 50. FIGs. 13A-G show anteroposterior and lateromedial views of the examples of lead placement of FIG. 12 and ranges of angles for stimulating lead insertion taking into consideration bony structures of the spine, not including soft tissues (e.g., muscle, fat, connective tissue, etc.) and illustrating the multitude of insertion approaches possible for the placement of a stimulating lead 50.

[0232] In FIGs. 13 A-G, the solid arrow represents the trajectory of the lead 50 insertion (e.g., at angles 62) for each approach in the anteroposterior view (left) and lateromedial view (right). The dotted lines represent variation in the same technique (e.g., within 30 degrees of the target insertion angle). Exemplary approaches include (A) perpendicular to the skin (90 degrees), (B) a inferosuperior 45 degree angle, (C) a superoinferior 135 degree angle, (D) lateromedial 45 degree angle, (E) a inferosuperior and lateromedial 45 degree angle, (F) a superoinferior and lateromedial 135 degree angle, and (G) a superoinferior and mediolateral 45 degree angle. Generally, the approach in FIG. 13 A having a perpendicular angle may result in higher muscular 20 forces exerted on the lead 50 compared to the other approaches, see FIG. 12A. Similarly, the approaches in FIGs. 12B, D, and E having an angle contrary to the angles of the musculature 20 may result higher muscular 20 forces exerted on the lead 50 compared to the other approaches. FIGs. 12C and F, being aligned with the angles of the musculature 20 may result lower muscular 20 forces exerted on the lead 50 and improved lead 50 outcomes compared to the other approaches.

[0233] It is noted that other considerations may also affect the recommended approach, see FIG. 24, for example, and may result in recommended approaches that may not necessarily have the most aligned angle of insertion, but may satisfy other considerations such as insertion location on the body, location of target stimulation site, patient anatomy, healing, and the like.

[0234] FIGs. 14A-C show an embodiment of orienting a lead 50 such that the longitudinal axis of the lead 50 is parallel or mostly parallel with the orientation of the muscles 20 that the lead intersects and the resulting lead shape at rest and during muscle change. In an embodiment, the position of the lead 50 may enable the lead 50 to reversibly change lead-shape in response to forces applied on the lead 50 , thus avoiding lead fracture, dislodgement, and migration.

[0235] FIGs. 14D-F show an embodiment of partial alignment of the lead 50 with the orientation of the muscles 20 that the lead intersects increases shear forces at the boundaries of the muscle bundles and the resulting lead shape at rest and during muscle change. In an embodiment, this position of the lead 50 may increase the likelihood of treatment interruption. FIGs. 14H-J show an embodiment of placing the lead50 with the orientation that is orthogonal to the orientation of the muscles 20 that the lead intersects maximizes or further increases shear forces at the boundaries of the muscle bundles 20. In an embodiment, the position of the lead 50 may maximize or increase the likelihood of treatment interruption via lead fracture, dislodgement, and / or migration.

[0236] FIGs. 15A-D show several embodiments of lead 50 trajectories with respect to muscle bundle 20 orientation (e.g., fascicles) when inserted for placement to target a nerve 10 with electrical stimulation (e.g., demonstrating multiple possible lead insertion trajectories in which the region of activation generated from the electrode encompasses the target nerve). In FIG. 15 A, the longitudinal axis of the lead 50 (e.g., the elastic and / or compliant portion of the lead) is primarily aligned with the direction of the muscle bundles. In FIG. 15B, the longitudinal axis of the lead 50 (e.g., the elastic and / or compliant portion of the lead) is generally (e.g., mostly) aligned with the direction of the muscle bundles. In FIG. 15C, the longitudinal axis of the lead 50 (e.g., the elastic and / or compliant portion of the lead) is generally (e.g., mostly) not aligned (e.g., orthogonal) with the direction of the muscle bundles.In FIG. 15D, the longitudinal axis of the lead 50 (e.g., the elastic and / or compliant portion of the lead) is primarily not aligned (e.g., orthogonal) with the direction of the muscle bundles.

[0237] FIGs. 16A-D shows the magnitude of fracture-causing forces from muscle 20 acting on the lead 50 based on lead 50 orientation within muscle 20. As shown in FIG. 16A, the magnitude of fracture-causing forces is least when the longitudinal axis of the lead 50 is parallel to the orientation of the muscle bundles (e.g., muscles, muscle planes, muscle fascicles, muscle fibers). As shown in FIG. 16B, the magnitude of fracture-causing forces on the lead 50 increases, but remains low, when the longitudinal axis of the lead 50 is generally aligned (e.g., within 30 degrees) with the orientation of the muscle bundles 20 (e.g., muscles, muscle planes, muscle fascicles, muscle fibers). As shown in FIG. 16C, the magnitude of fracture-causing forces on the lead 50 is high when the longitudinal axis of the lead is generally not aligned with the orientation of the muscle bundles 20 (e.g., muscles, muscle planes, muscle fascicles, muscle fibers). As shown in FIG. 16D, the magnitude of fracture-causing forces on the lead 50 is maximal when the longitudinal axis of the lead 50 is orthogonal (i.e., perpendicular) to the orientation of the muscle bundles 20 (e.g., muscles, muscle planes, muscle fascicles, muscle fibers). It is to be appreciated that as the magnitude of fracture-causing forces increases, the likelihood that the lead 50 remains intact for the prescribed therapeutic treatment reduces.

[0238] FIG. 17A-C shows the disclosed systems and methods as applied to lumbar lead placement. In an embodiment, as shown in FIG. 17A, a physician may use best clinical practices (e.g., imaging, anatomical reference points, anatomy book) to determine the muscle line of action and / or net force and / or net movement of the muscles 20 that the lead 50 will intersect. As shown in FIG. 17B, the physician may then inset an introducer needle (loaded with a lead 50) such that the orientation of the introducer needle and lead 50 is aligned with the orientation of the muscle line of action and / or net force and / or net movement of the muscles 20 that the lead 50 will intersect in a desired and similar orientation. As shown in FIG. 17C,after deployment of the lead 50, the longitudinal axis of the lead 50 is aligned with the paraspinal muscles 20. In an embodiment, this position of the lead 50 may avoid lead fracture, dislodgment, and migration and enable the successful completion of the prescribed therapy.

[0239] Generally, the disclosed systems and methods 100 wherein a lead 50 is positioned generally aligned with the orientation of muscle bundles 20 or is otherwise positioned in a way that minimizes acting forces on the lead 50 can reduce the incidence of fracture, dislodgment, and / or migration of the lead 50 during muscle bundle 20 change. For example, FIGS. 18A-D illustrate a coiled lead 50 with the longitudinal axis of the lead 50 aligned (i.e., parallel or mostly parallel or within 30 degrees of parallel) with the orientation of muscle bundles 20 (e.g., muscles, muscle planes, muscle fascicles, muscle fibers). From rest, shown in FIG. 18 A, the coiled lead 50 aligned with the orientation of muscle bundles 20 may avoid fracture, dislodgment, and migration during muscle bundle 20 change in length (FIG. 18B), rotation or change in angle (FIG. 18C), and change in thickness (FIG. 18D).

[0240] On the other hand, conventional systems and methods wherein a lead 50 may be positioned generally orthogonally or perpendicular to the orientation of muscle bundles 20 or is otherwise positioned in a way that results in significant acting forces on the lead 50 (e.g., above a threshold tolerance of the lead 50) can result in the fracture, dislodgment, and / or migration of the lead 50 during muscle bundle 20 change. For example, FIG. 18E-H illustrate a coiled lead with the longitudinal axis of the lead 50 not aligned (e.g., mostly or partially orthogonal or perpendicular) with the orientation of muscle bundles 20 (e.g., muscles, muscle planes, muscle fascicles, muscle fibers). From rest, shown in FIG. 18E, the coiled lead 50 aligned with the orientation of muscle bundles 20 may experience fracture, dislodgment, and / or migration during muscle bundle 20 change in length (FIG. 18F), rotation or change in angle (FIG. 18G), and change in thickness (FIG. 18H) due to forces and / or differential movement at the boundary conditions of the muscle bundles 20. These increased forces acting on the lead50 and the risk of fracture, dislodgment, and / or migration during muscle bundle 20 change can limit efficacy of the electrical stimulation treatment and limit life of the lead 50.

[0241] In another example, FIGS. 19A-D illustrate a non-coiled lead 50 with the longitudinal axis of the lead 50 aligned (i.e., parallel or mostly parallel or within 30 degrees of parallel) with the orientation of muscle bundles 20 (e.g., muscles, muscle planes, muscle fascicles, muscle fibers). From rest, as shown in FIG. 19A, the non-coiled lead 50 aligned with the orientation of muscle bundles 20 may avoid fracture, dislodgment, and migration during muscle bundle 20 change in length (FIG. 19B), rotation or change in angle (FIG. 19C), and change in thickness (FIG. 19D).

[0242] In another example, FIGS. 19E-H illustrate a non-coiled lead 50 with the longitudinal axis of the lead 50 not aligned (e.g., mostly or partially orthogonal or perpendicular) with the orientation of muscle bundles 20 (e.g., muscles, muscle planes, muscle fascicles, muscle fibers). From rest, shown in FIG. 19E, the non-coiled lead 50 aligned with the orientation of muscle bundles 20 can experience fracture, dislodgment, and / or migration during muscle bundle 20 change in length (FIG. 19F), rotation or change in angle (FIG. 19G), and change in thickness (FIG. 19H) due to forces and / or differential movement at the boundary conditions of the muscle bundles 20. These increased forces acting on the lead 50 and the risk of fracture, dislodgment, and / or migration during muscle bundle 20 change can limit efficacy of the electrical stimulation treatment and limit life of the lead 50.

[0243] As shown in FIG. 18, showing an embodiment with a coiled lead 50, and FIG. 19, showing an embodiment with a non-coiled lead 50, the alignment of both leads 50 with muscle 20 orientation may have the same or similar effect in preventing fracture, dislodgment, and / or migration during muscle bundle 20 change and increasing life span of the leads 50, see FIGs. 18A-D and 19A-D, compared to positions of the leads 50 where they are not aligned with muscle 20 orientation (but are rather perpendicular or orthogonal to the muscle bundles20, in an example), which can result in the fracture, dislodgment, and / or migration during muscle bundle 20 change and decrease life span of the leads 50, see FIGs. 18E-Hand 19E-H. That is, the disclosed systems and methods 100 may be used with any lead type to achieve improved longevity of the leads 50 and to decrease risk of complications during muscle change.

[0244] Similar to FIG. 1 A, FIG. 20 A depicts a schematic anatomic view of the lumbar spine in the anterior-posterior view, with paraspinal muscle (e.g., multifidi) bundles 20 (e.g., muscles, muscle fascicles, muscle fibers, muscle planes) primarily starting cephalad and terminating caudad. The lumbar medial branch of the dorsal ramus nerve or target nerve 10 may originate near the superior articular process and run between the superior articular process and the transverse process of the vertebral body caudad.

[0245] FIGs. 20B and 20F show embodiments of a lead 50 (e.g., a coiled lead in FIG. 20B and a non-coiled lead in FIG. 20F) including one or more electrodes 53 inserted into the lumbar spine region of the body 5 to stimulate the target nerve 10. In an embodiment, lead 50 and position of lead 50 may be generally aligned with the muscle bundle 20 (e.g., the muscle line of action). In an embodiment, lead 50 and position of lead 50 prevents interruption of therapeutic delivery causes by lead fracture, migration, and / or displacement by intentionally and reversibly changing lead-shape in response to forces applied on the lead 50.

[0246] Here, as shown in FIG. 20C, an internal pulse generator (IPG) with a coiled lead 50 (e.g., closed coiled) may be implanted and placed such that the longitudinal axis of the lead, with initial shape L , is primarily aligned with muscle bundles 20 at rest (LMI). AS shown in FIG. 20D, during muscle contraction or musculoskeletal compression (LM2), the lead 50 avoids fracture, migration, and / or displacement by changing shape (LL2). AS shown in FIG. 20E, during muscle elongation or musculoskeletal tension (LM3), the lead 50 avoids fracture, migration, and / or displacement by changing shape (LL3). AS described herein, it is appreciatedthat the disclosed systems and methods 100 may include coiled and non-coiled leads having the same or similar results in lead efficacy.

[0247] For example, as shown in FIG. 20G, an internal pulse generator (IPG) with a non-coiled lead 50 (e.g., lead with mechanical favorability in one or more axis) may be implanted and placed such that the longitudinal axis of the lead, with initial shape LLX, is primarily aligned with muscle bundles 20 at rest (LMX). AS shown in FIG. 20H, during muscle contraction or musculoskeletal compression (LMy), the lead 50 avoids fracture, migration, and / or displacement by changing shape (Liy). As shown in FIG. 201, during muscle elongation or musculoskeletal tension (LMZ), the lead 50 avoids fracture, migration, and / or displacement by changing shape (LLZ).

[0248] As shown in FIG. 20J, as an example of the present invention, an internal pulse generator (IPG) with a non-coiled lead (e.g., lead with or without mechanical favorability in one or more axis) is implanted and placed such that the longitudinal access of the lead, with initial shape LLX, is primarily aligned with muscle bundles at rest (LMX). AS shown in FIG. 20L, during muscle contraction or musculoskeletal compression (LMy), the lead avoids fracture, migration, and / or displacement by aligning with the musculoskeletal system (L y). As shown in FIG. 20M, during muscle elongation or musculoskeletal tension (LMZ), the lead avoids fracture, migration, and / or displacement by aligning with the musculoskeletal system (LLZ).

[0249] As described herein, the discloses systems and methods 100 may be used for lumbar lead placement. For example, FIG. 21 illustrates an embodiment of a lead 50 targeting the lumbar medial branch oriented such that the angle of the lead 50 is primarily parallel with the net forces and / or net movement of the paraspinal muscles 20 (e.g., multifidi). In an embodiment, the lead 50 targeting the lumbar medial branch is placed at a 120-150 degree cephalad to caudad angle (e.g., the angle 64 from the plane defined by the skin at the area ofinsertion) to align with the paraspinal muscles 20 and net force and avoid lead fracture, lead migration, and lead dislodgment. It is appreciated that in other embodiments, a lead targeting the lumbar medial branch could be placed at other angles with other trajectories to minimize the deleterious musculoskeletal forces acting on the lead. For example, other considerations 150 such as site of insertion may modify the angle or trajectories of the lead, or imaging or physical assessment may show an individual’s paraspinal muscles have a different orientation or angle of force.

[0250] For a percutaneous system, bandaging location of the lead exit site may be considered for patient comfort and cleanliness. When leads are placed in or near the low back, see FIG. 22A, while aligning the lead 50 with the muscles 20 can be accomplished either with a caudad-cephalad approach or cephalad-caudad approach (needle trajectory), the caudad- cephalad approach requires bandaging on the buttocks and underneath the waistline, which in some patients causes discomfort and in some introduces cleanliness challenges with a bandage over the intergluteal cleft. When bilateral leads are placed along the spine, see FIG. 22B, it is may be preferred for patient comfort to have one bandage covering both lead exit sites, as opposed to two bandages. Thus, the placement of lead 50 exit sites near enough to the midline such that both sites can fit under one bandage may be preferred than lead exit sites farther from the midline such that two bandages are used.

[0251] It is noted that while bandaging and sites of entrance and insertion of the leads may be considered when determining the angle of insertion relative the muscle orientation for the intended target site of electrical stimulation that the angle of insertion relative the muscle orientation for the intended target site of electrical stimulation may in turn be considered when determining the sites of entrance and insertion of the leads and resulting bandages. Under different circumstances, e.g., different patients anatomies, preferences, etc., either consideration may be prioritized over the other and result in different sites or angles of leadinsertion. Bandage sites, healing, and location of entrance and exit sites may be considerations in determining desired lead placement but may not necessarily be determinative as other considerations may also be used in the determination such as the angle of insertion relative the muscle orientation.

[0252] Similarly, when leads 50 are placed in or near the neck, see FIG. 23 A, while aligning the lead 50 with the muscles 20 can be accomplished either with a caudad-cephalad approach or cephalad-caudad approach (needle trajectory), the cephalad-caudad approach requires banding over the hairline, where the adhesive may not create a sanitary seal with the skin, and thus may be less preferred. Placement with a caudad-cephalad approach may orient the leads 50 in such a way that aligns with muscle bundles 20 to avoid lead fracture and migration with an external system (FIG. 23B) or permanently placed system (FIG. 23 C). As described herein, bandage sites, healing, and location of entrance and exit sites may also be a consideration 150 in determining the angle and position of lead insertion relative the muscle orientation for the intended target site of electrical stimulation.

[0253] For example, FIG. 24 represents a non-exhaustive chart of considerations 150 for the optimization of lead orientation such that the optimization satisfies the plurality or majority of conditions, in an embodiment, thus maximizing the effectiveness of the system (e.g., pain relief) and minimizing the potential for treatment interruptions (e.g., lead dislodgement, lead migration, lead fracture) or sub -therapeutic treatment (e.g., due to patient discomfort or poor compliance), enabling the disclosed systems and methods 100 to modulate central neural processing to reduce the perception of pain. The considerations 150 may be implemented or assessed manually, e.g., by a physician or that may be implemented through computer instructions or artificial intelligence analysis. The considerations 150 may include reference to historical or population data such as general anatomy across persons, may be basedon physical assessment by a physician to a specific patient, may be based on patient-specific imaging, and the like.

[0254] In an embodiment, the considerations 150 may include that musculoskeletal modeling interrogates lead orientations that minimize the number of muscles intersected, minimizes the difference in angle between the lead and the muscles, and minimizes the magnitude of force generated from those muscles. In an embodiment, the considerations 150 may include that lead orientation avoids sensitive structures (e.g., epidural space, arteries, direct contact with nerves). In an embodiment, the considerations 150 may include that lead orientation avoids bony structures (e.g., transverse process). In an embodiment, the considerations 150 may include that lead orientation places the lead exit site and bandaging in a location that minimizes subject discomfort and avoids delicate areas (e.g., hairline or buttocks). In an embodiment, the considerations 150 may include that maximizing the effectiveness of the system while minimizing the potential for treatment interruptions enables the present system and method to modulate central neural processing to reduce the perception of pain. In an embodiment, the considerations 150 may include that identify possible lead orientations with the electrode position remote from the target nerve such that stimulation produces comfortable sensations focally in the region(s) of pain. In an embodiment, the considerations 150 may include that lead orientation makes certain the distance from the skin to the target area is long enough to avoid dislodgement (e.g., > 4cm), but is shorter than the total lead length (e.g., < 10cm). In an embodiment, the considerations 150 may include that lead orientation avoids causing undue discomfort (e.g., area sensitive to allodynia, off-target stimulation). In an embodiment, the considerations 150 may include that lead orientation accounts for interpatient anatomical variation while avoiding potential complications from approaches that require extreme specificity. In an embodiment, the considerations 150 may include that lead orientation maximizes the ease of placement of the physician and maximizesthe repeatability of placement by the physician, while minimizing the discomfort of the procedure on the patient.

[0255] In an embodiment, the result of the considerations 150 may include optimizing the orientation of the lead to satisfy the plurality or majority of conditions, thus maximizing the effectiveness of the system (e.g., pain relief) and minimizing the potential for treatment interruptions (e.g., lead dislodgement, lead migration, lead fracture) or sub-therapeutic treatment (e.g., due to patient discomfort or poor compliance).

[0256] FIGS. 25A-B shows an exemplary execution of the non-exhaustive list of considerations 150 used in FIG. 24 and a recommended output based on the region of the body which may lead to different recommended approaches based on the region of the body. As shown in FIG. 25 A, a lead targeting the cervical medial branch nerves inferosuperiorly angled at 30-60 degrees (e.g., the angle 64 from the plane defined by the skin at the area of insertion) satisfies the plurality or majority of conditions, thus maximizing the effectiveness of the system (e.g., pain relief) and minimizing the potential for treatment interruptions (e.g., lead dislodgement, lead migration, lead fracture) or sub -therapeutic treatment (e.g., due to patient discomfort or poor compliance), enabling the present system and method to modulate central neural processing to reduce the perception of pain, see also FIG. 32, for example. As shown in FIG. 25B, a lead targeting the lumbar medial branch nerves superoinferiorly angled at 120-150 degrees (e.g., the angle 64 from the plane defined by the skin at the area of insertion) satisfies the plurality or majority of conditions, thus maximizing the effectiveness of the system (e.g., pain relief) and minimizing the potential for treatment interruptions (e.g., lead dislodgement, lead migration, lead fracture) or sub -therapeutic treatment (e.g., due to patient discomfort or poor compliance), enabling the present system and method to modulate central neural processing to reduce the perception of pain, see also FIG. 21, for example.

[0257] FIG. 26A-C show, respectively, anterior-posterior view, oblique view, and lateral views of a needle introducer of a percutaneous lead targeting the lumbar medial branch nerves for the treatment of low back pain and considerations for positions of insertion. In approach 1, the needle successfully navigates anatomical features (e.g., bone) to reach the therapeutic target, while in approach 2, the needle path is blocked by anatomical features (e.g., transverse spinous process). Anatomical features such as bones may prevent optimal alignment of a lead with muscle. As described herein, anatomy and bony structures may also be a consideration 150 in determining the angle and position of lead insertion relative the muscle orientation for the intended target site of electrical stimulation.

[0258] FIGS. 27A-F show data relating to the rate of treatment interruption for existing and strengthened leads 50 and positioning of the leads 50 relative the muscle orientation 20 (e.g., aligned versus not aligned) FIGS. 27A-F show how lead design and insertion approach impacts the rate of lead interruption (e.g., lead fracture or migration) and thus the rate of lead survival for the entirety of the prescribed treatment period. Wherein Xi is “X” rate of fracture interruption and Xs is “X” rate of survival of the lead for the entire desired therapeutic treatment period. Wherein an approach with an original lead inserted in an approach that is not aligned to the direction of muscle forces and movement has a slightly higher (i.e., more fractures and or migrations) rate of treatment interruption than an approach with a strengthened lead that is inserted in an approach that is not aligned to the direction of the muscle forces and movement, and a significantly higher (i.e., more fractures and / or migrations) than a lead that is designed to reversibly change lead-shape in response to forces applied on the lead that is inserted in an approach that is sufficiently aligned with the direction of the net force and movement of the musculoskeletal system. An approach that aligns the longitudinal axis of the lead with the direction of net force and movement of the musculoskeletal systems results in significantly lower rate of treatment interruption and likelihood for survival of the lead for theprescribed therapeutic treatment period, compared to both the standard lead and strengthened lead when inserted in an approach that is not aligned to the direction of the muscle forces and movement.

[0259] FIGS. 28A-Q illustrates non-limiting embodiments of stimulating leads 50 for use with the disclosed systems and methods 100 of peripheral nerve stimulation for insertion into a portion of the body such that the longitudinal axis of the lead 50 is sufficiently aligned with the direction of net force and movement by the musculoskeletal system 50 in the implanted bodily region to avoid lead fracture or migration to prevent interruption of therapeutic delivery of electrical stimulation to a nerve 10. As described herein, any lead type and aspects thereof may be considered when determining the angle of insertion relative the muscle orientation for the intended target site of electrical stimulation with other considerations such as the angle of insertion relative the muscle orientation. It is noted that any lead may be used with the disclosed systems and methods 100 and show improved results related to lead longevity and resistance to undesired movement when the leads are placed using the disclosed systems and methods 100 such as when aligning the lead with the muscle orientation for the intended target site of electrical stimulation and assessing other considerations 150, such as part of the body, patient anatomy, etc., to determine lead placement (e.g., the angle 64 from the plane defined by the skin at the area of insertion).

[0260] FIGS. 29 A-D illustrate non-limiting embodiments of a curved introducer needle for a percutaneous lead 50 placement in various positions on the spine, shown in example B) in the cervical spine, C) in the lumbar spine, and D) sacral spine may improve the ability to place a lead 50 near the spine due to the curvature of the spine. As shown, the type and shape of introducer may also be a consideration 150 in determining the angle and position of lead insertion relative the muscle orientation for the intended target site of electrical stimulation.

[0261] FIGS. 30A shows an embodiment of a needle, lead, and / or electrode 50 for insertion with a fixed length. As shown in FIG. 3 OB, in an embodiment, it may not be not possible to insert the needle, lead, and / or electrode 50 with a fixed length into a muscle such that the needle, lead, and / or electrode reach the therapeutic target (indicated by a circle) while still being aligned with the orientation of the muscle bundle 20 (e.g., muscle, muscle bundle, muscle plane, muscle fascicle, and / or muscle fiber). As such, as shown in FIG. 30C, the disclosed systems and methods 100 teach that primarily aligning the needle, lead, and / or electrode 50 with the orientation of the muscle bundle 20 (e.g., the longitudinal axis of the lead 50 is within 5, 10, 15, 20, 25, 30, 35, 40, 45 degrees parallel to the axis of the muscle bundle 20) enables delivery of therapeutic stimulation while avoiding fracture, migration, and dislodgment. As shown, the length of the lead may also be a consideration 150 in determining the angle and position of lead insertion relative the muscle orientation for the intended target site of electrical stimulation.

[0262] FIGS. 31A-I illustrates non-limiting embodiments of lead 50 trajectories to stimulate peripheral nerves for the treatment of pain in and around the spine. FIG. 31A illustrates anatomical dermatome boundaries of a human. As shown, intended stimulation site and target nerve 10 may also be a consideration 150 in determining the angle and position of lead insertion relative the muscle orientation for the intended target site of electrical stimulation.

[0263] In an embodiment, FIGS. 3 IB and 3 IF illustrate an example of bilateral leads placed inferosuperiorly to target the cervical medial branch nerves for the treatment of head and neck pain. An inferosuperior lead trajectory places the leads below the hairline, increases the amount of lead under the skin to minimize dislodgement, and places the leads in line with the muscle bundles to avoid fracture, migration, and dislodgement.

[0264] In an embodiment, FIGS. 31C and 31G illustrate an example of bilateral leads placed superoinferiorly to target the lumbar medial branch nerves for the treatment of low back pain. A superoinferior lead trajectory places the leads above the waistline, increases the amount of lead under the skin to minimize dislodgement, and places the leads in line with the muscle bundles to avoid fracture, migration, and dislodgement.

[0265] In an embodiment, FIGS. 3 ID and 31H illustrate an example of two leads placed superoinferiorly with one lead targeting the lumbar medial branch nerves for low back pain and one lead targeting the lumbar spinal nerve for low back pain and leg pain. A superoinferior lead trajectory places the leads above the waistline, increases the amount of lead under the skin to minimize dislodgement, and places the leads in line with the muscle bundles to avoid fracture, migration, and dislodgement.

[0266] In an embodiment, FIGS. 3 IE and 311 illustrate an example of two leads bilaterally placed superoinferiorly targeting the sacral lateral branches to relieve pain at or around the sacroiliac joint or at or around the buttocks. It is appreciated that the disclosed systems and methods 100 teach that pain at or around the sacroiliac joint or at or around the buttocks can also be alleviated by targeting the cluneal branches. For sacral lateral branch or cluneal nerve targets, a superoinferior lead trajectory places the leads above the waistline, increases the amount of lead under the skin to minimize dislodgement, and places the leads in line with the muscle bundles to avoid fracture, migration, and dislodgement.

[0267] As described herein, the discloses systems and methods 100 may be used for cervical lead placement. For example, FIG. 32 illustrates an embodiment of a lead 50 targeting the cervical medial branch oriented such that the angle of the lead 50 is primarily parallel with the net forces and / or net movement of the paraspinal muscles 20 and surrounding musculoskeletal architecture. In an embodiment, the lead 50 targeting the cervical medial branch is placed at a 30-60 degree caudad to cephalad angle (e.g., the angle 64 from the planedefined by the skin at the area of insertion) to align with the paraspinal muscles 20 and net force and avoid lead fracture, lead migration, and lead dislodgment. It is appreciated that in other embodiments, a lead targeting the cervical medial branch could be placed at other angles or with other trajectories to minimize the deleterious musculoskeletal forces acting on the lead. For example, other considerations 150 such as site of insertion may modify the angle or trajectories of the lead, or imaging or physical assessment may show an individual’s paraspinal muscles have a different orientation or angle of force.

[0268] FIG. 33A illustrates exemplary approaches for the orientation of a lead. For example, approaches include (orientation A) perpendicular to the skin (90 degrees), (orientation B) a inferosuperior 45 degree angle, (orientation C) a superoinferior 135 degree angle, (orientation D) lateromedial 45 degree angle, (orientation E) a inferosuperior and lateromedial 45 degree angle, (orientation F) a superoinferior and lateromedial 135 degree angle, and (orientation G) a superoinferior and mediolateral 45 degree angle. FIGs. 33B-D show related considerations 150 of the lead placements in FIG. 33 A including aligning the lead with the angle of the muscle bundles, aligning the lead so that it passes through muscles with the least amount of force, and aligning the lead in the direction of muscle net forces for each lead placement and their respective outcome and lead life.

[0269] A biophysical model of the structures the lead 50 intersects or passes through can determine which orientation minimizes the difference between the lead 50 angle and the angle of the muscles bundles 20 it intersects, the total force of the muscles 20 that the lead 50 intersects, and the difference between the lead 50 angle and the net force vector of the muscles 20. As shown in FIGs. 33B the biophysical model determined that for a lumbar medial branch nerve target for the treatment of low back pain, a superoinferior 135-degree angle (orientation C) (e.g., the angle 64 from the plane defined by the skin at the area of insertion) lead 50 orientation successfully optimizes the placement of lead 50 for therapeutic delivery ofstimulation while avoiding lead fracture, lead migration, and lead dislodgment. As shown in FIG. 33C, a superoinferior 135-degree angle (orientation C) minimizes lead fracture rate and lead migration rate towards a significantly greater lead survival rate. As shown in FIG. 33D, optimizing lead orientation while avoiding fracture and migration enables lead longevity and successfully completion of prescribed cycles. The biophysical model and considerations 150 may be implemented or assessed manually, e.g., by a physician or that may be implemented through computer instructions or artificial intelligence analysis. The considerations 150 may include reference to historical or population data such as general anatomy across persons, may be based on physical assessment by a physician to a specific patient, may be based on patientspecific imaging, and the like.

[0270] FIGS. 34A-D show non-exhaustive examples of electrode placement targeting peripheral spinal nerves and expected areas of pain relief (FIG. 34A: placement at T12 spinal nerve, FIG. 34B: placement at C6 and C7 spinal nerves, FIG. 34C: placement at L4 spinal nerve, FIG. 34D: placement at T5 and T6 spinal nerves). As shown, intended stimulation site and target nerve 10 may also be a consideration 150 in determining the angle and position of lead insertion relative the muscle orientation for the intended target site of electrical stimulation.

[0271] FIG. 35 shows non -limiting examples of a troubleshooting table 160 for assessing lead 50 placement that may be utilized as part of the discloses systems and methods 100 , for example, associated with a percutaneous stimulation system in the lumbar paravertebral space in accordance with various embodiments described herein. The troubleshooting table 160 may be implemented or assessed manually, e.g., by a physician or that may be implemented through computer instructions or artificial intelligence analysis.

[0272] FIG. 36A illustrates example placement of a percutaneous coiled lead 50 to treat pain around the cervical spine, placed in alignment with the primary muscle line of action.FIGs 36B-E illustrate examples of lead 50 aligned with the primary muscle line of action 20 and / or net vector and the secondary muscle line 20’ of action and / or net vector for the treatment of pain around the cervical spine.

[0273] FIGS. 37A-B show exemplary schematics of ultrasound imaging when targeting the lumbar medial branch nerves and placement of a lead 50 based on the imaging. In an embodiment, FIG. 37A illustrates a 90-degree approach, where the orientation of the lead 50 does not align with the orientation of the muscle 20, and thus movement or forces exerted by the musculoskeletal system have a greater likelihood of causing treatment interruption (e.g., lead fracture, dislodgment, or migration). Alternatively, in an embodiment shown in FIG. 37B, the needle path and / or lead 50 path is aligned with the orientation of the muscle 20, and thus the reversable, elastic, and compliant properties of the lead 50 can successfully navigate any movement or forces exerted by the musculoskeletal system, resulting in completion of the prescribed therapy. As described herein, the disclosed systems and methods 100 may utilize imaging to assess a particular morphology or anatomy of a patient (e.g., the orientation of muscle bundles 20, location of target nerves 10, muscles needed to traverse to access target area of stimulation 7, location of bony structures, other physiological structures and locations, and the like which may determine or inform lead 50 angle and placement.

[0274] FIG. 38 shows data for the fracture rate, migration rate, and lead survival rate for various leads and orientations of the leads 50. A conventional lead, which may be rigid or non-rigid, that is placed into the musculoskeletal system, but is not aligned with the net forces and / or movement of the structures that the lead intersects, is prone to increased fracture and migration rate, thus leading to a reduction in lead survival rate (i.e., the therapy is prematurely interrupted).

[0275] Alternatively, consistent with the disclosed systems and methods 100, a conventional lead 50 that is sufficiently oriented with the direction of net forces and / ormovement of the structure 20 that the lead 50 intersects had a significantly lower fracture rate and migration rate and a significantly higher lead survival rate than a conventional lead that is not aligned with the net forces and / or movement of the structures that the lead intersects.

[0276] A lead 50 that is designed to reversibly change lead-shape in one or more dimensions in response to forces applied on the lead 50 (e.g., a coiled lead) that is placed into the musculoskeletal system, but is not aligned with the net forces and / or movement of the structures 20 that the lead 50 intersects, has a lower fracture rate and migration rate and higher lead survival rate than a conventional lead that is not aligned with the net forces and / or movement of the structures that the lead intersects and a similar fracture rate, migration rate and higher lead survival rate to a conventional lead that is aligned with the net forces and / or movement of the structures that the lead intersects.

[0277] Finally, a lead 50 that is designed to reversibly change lead-shape in one or more dimensions in response to forces applied on the lead (e.g., a coiled lead) that is placed into the musculoskeletal system and is aligned with the net forces and / or movement of the structures 20 that the lead intersects has an extremely low fracture rate and migration rate (i.e., significantly lower than a conventional lead not oriented with the net forces and / or movement, a conventional lead that is oriented with the net forces and / or movement, and a lead that is designed to reversibly change lead-shape in one or more dimensions in response to forces applied on the lead (e.g., a coiled lead) that is oriented with the net forces and / or movement), thus leading the a significantly higher lead survival rate and likelihood of completing the prescribed treatment.

[0278] FIGS. 39A-H show additional views of the examples of lead 50 placement and angles for stimulating lead insertion taking into consideration anatomical structures.

[0279] In addition to variations in the architecture within muscle, the stimulation system must navigate the architecture between and around muscles. As a non-limiting example,for a percutaneous lead to be placed from the skin to a location near the lumbar vertebral lamina, the lead would traverse the epidermis, dermis, hypodermis, thoracolumbar fascia, the erector spinae muscles and their connective tissues, and the multifidus muscle and their connective tissues. Each layer that the lead intersects is in constantly unsynchronized motion, creating shear forces at the intersection of each boundary (FIG. 7). Additionally, those shear forces may be magnified (increased, made larger) when a lead crosses two or more muscles or muscle layers if one muscle is contracting in a way that differs from another muscle. As a nonlimiting example, if a lead and / or electrode(s) on the lead spans more than one muscle (e.g., muscle X, muscle Y) and muscle X is actively shortening and muscle Y is actively isometric or maintaining length, there would be an increase in the amount of shear forces at or near the boundaries or intersection of muscle X and muscle Y. It is appreciated that muscle X may be actively lengthening, actively shortening, or actively isometric and muscle Y may be actively lengthening, actively shortening, or actively isometric. If the mechanics or dynamics of muscle X are not the same as muscle Y, a lead that spans both muscle X and muscle Y will undergo significant shear forces at, between, and / or near the boundaries of muscle X and muscle Y. In another example, the mechanics or dynamics of muscle X and muscle Y may be the same (e.g., muscle X and muscle Y are lengthening or muscle X and muscle Y are shortening) but still have considerable shear forces between or near the boundaries of muscle X and muscle Y because the dynamics of one muscle is greater than the dynamics of another muscle (e.g., muscle X is lengthening at a quicker rate than muscle Y). As an example, the present invention teaches that placing a flexible lead (e.g., a coiled lead designed to stretch along a specified direction or axis) parallel, nearly parallel, or in line with the relative orientation (e.g., pennation angle) of the muscle fascicles of every, most, or the plurality of muscles enables the lead to stretch, elongate, expand, shorten, constrict or otherwise change length of shape while avoiding shear forces between the muscles or near the boundaries of the muscles or in the muscles thatgenerate the most force (FIGs. 8-11). The present invention teaches that, when it is not possible to be parallel, nearly parallel, or in line with the relative orientation (e.g., pennation angle) of multiple muscles that the lead intersects, the lead should be parallel, nearly parallel, or in line with the relative orientation (e.g., pennation angle) of the muscle with the greatest potential detrimental effect on the lead (e.g., force generating capacity, shape change, excursion, bulging). As an example, as shown in FIGs. 8-11, if a lead intersects both muscle A and muscle B, with muscle B have a larger force generating capacity than muscle A, the lead should be placed parallel, nearly parallel, or in line with the relative orientation (e.g., pennation angle) of muscle B if it is not possible to be aligned with the force vectors and the axis with changes in length of both muscles.

[0280] The present system, device, method, and instructions for use of systems, devices, and methods teach that optimizing the orientation of the lead and / or electrode can be achieved by modeling the number of structures (e.g., muscles) the lead and / or electrode intersect or pass through, the forces generated by the muscles the lead and / or electrode intersect or pass through, and the directionality of those forces in relation to the orientation of the lead and / or electrode. As an example, the orientation, placement, or path of lead and / or electrode may be specifically chosen so the movement of surrounding structures (e.g., muscles) causes the lead to displace, shorten, lengthen, translate in one or more planes (e.g., sagittal, coronal, transverse) with respect to the body, lead, and / or electrode while limiting displacement, length change, or translation in one or more other planes (e.g., sagittal, coronal, transverse) with respect to the body, lead, and / or electrode. In an embodiment, a dynamic musculoskeletal model of the spine, which features 7 cervical vertebrae, 12 thoracic vertebrae, 5 lumbar vertebrae, a sacral vertebrae, over 500 musculotendon actuators, 8 main paraspinal muscle groups (i.e., rectus abdominis, external obliques, internal obliques, erector spinae, multifidus, quadrates lumborum, psoas major, and latissimus dorsi), multiple cervical muscle groups (i.e.,trapezius, semispinalis capitis, longissimus capitis), and 6 degrees-of freedom at each joint, informs the orientation, placement, or path of the percutaneous needle and / or electrode lead insertion. Model based muscle activation, muscle tension, and vertebral motion were previously validated against in-vivo measurements. As a non-limiting example, for each spinal level, the model interrogates the number of muscles intersected by the lead, the degree of parallelism between the lead and the muscles it intersects, and the force generating capacity of the muscles intersected by the lead at each of 7 orientations from skin to electrode location: (1) perpendicular to the skin (90 degrees), (2) a inferosuperior 45 degree angle, (3) a superoinferior 135 degree angle, (4) lateromedial 45 degree angle, (5) a inferosuperior and lateromedial 45 degree angle, (6) a superoinferior and lateromedial 135 degree angle, and (7) a superoinferior and mediolateral 45 degree angle (FIG. 12 and FIG. 13). In this non-limiting example for the treatment of lumbar spine pain, the target electrode location for each model interrogation and needle trajectory remains fixed at a location remote to the nerve along the course of the medial branch of the dorsal ramus as it lies medial and inferior to the facet joint. It is to be appreciated that additional lead orientations, different spinal levels, and alternative electrode targets along the nerves and its branches have been and can be interrogated further.

[0281] In a non-limiting example, for a lumbar medial branch of the dorsal ramus nerve target, the model reveals a superoinferior angle (cephalad-caudad) or inferosuperior angle (caudad-cephalad) of lead insertion decreases the number of intersecting muscle planes, minimizes the difference between the angle of the lead and / or electrode and the angle of the muscles it intersects, and reduces the peak force acting on the needle and / or electrode lead during movement (e.g., extension-flexion, axial rotation, and lateral bending) when compared to the alternative approaches modeled (e.g., a perpendicular 90 degree angle, lateromedial 45 degree angle, a inferosuperior and lateromedial 45 degree angle, a superoinferior and lateromedial 135 degree angle, and a superoinferior and mediolateral 135 degree angleorientation). In an embodiment, the present system and method utilizes a coiled lead design that, when positioned in a cephalad-caudad angle (superoinferior) or caudad-cephalad angle (inferosuperior) orientation, the body of the lead coils and uncoils (e.g., stretches or extends and relaxes) in the direction of muscle force while remaining secured in the tissue at the distal end of the lead (e.g., anchor) and avoiding forces or movements that cause lead migration, dislodgement, or fracture. In an embodiment, the present system and method utilizes a coiled lead design that, when positioned in a cephalad-caudad angle (superoinferior) orientation targeting the lumbar medial branch, the lead coils and uncoils (e.g., stretches or extends and relaxes) in the direction of muscle force while remaining secured in the tissue at the distal end of the lead (e.g., anchor) and avoiding forces or movements that cause lead migration, dislodgement, or fracture (FIG. 14). As an example, the method of electrode insertion may be specifically chosen so the movement of surrounding structures (e.g., muscles) causes the lead to coil and uncoil in the longitudinal direction of the coiled lead (FIG. 15). In this example, as shown in FIG. 16, coiling and uncoiling in the longitudinal direction would be advantageous because it would minimize movement in the transverse direction and decrease the magnitude of shear forces that can result in damage to the lead (e.g., fracture that prevents therapeutic stimulation delivery). As an example, as shown in FIG. 17 and FIG. 14, percutaneous placement of coiled leads may be inserted using a cephalad-caudad needle trajectory of 120- 150 degrees relative to the skin to mimic the musculoskeletal orientation near the lumbar spine (e.g., longitudinal muscle length, fascicle length, fiber length, pennation angle) of paraspinal muscles and other surrounding structures that largely connect at or near the posterior spinous process and largely terminate at or near the transverse spinous process (e.g., multifidus, iliocostalis, interspinales, rotator longus, rotator brevis, intertransversaii, and muscles of the erector spinae). In an embodiment, orienting the coiled lead (FIG. 18) in alignment with muscle bundles enables lead-shape change in response to muscle shortening, muscle lengthening,muscle rotation, muscle bulging, and muscle change in thickness, whereas placing the lead orthogonal or less parallel or less aligned with muscle bundles results in fracture or migration of the lead at the muscle bundle boundaries. In an embodiment, orienting the non-coiled lead (FIG. 19) in alignment with muscle bundles minimizes deleterious forces during muscle shortening, muscle lengthening, muscle rotation, muscle bulging, and muscle change in thickness, whereas placing the lead orthogonal or less parallel or less aligned with muscle bundles results in fracture or migration of the lead at the muscle bundle boundaries. In one embodiment, the present invention employs a cephalad-caudad (superoinferior) insertion trajectory to reduce muscle shearing forces and thus the risk of electrode fracture. It is appreciated that the present invention includes leads that change shape in the longitudinal direction, but also includes leads that change shape in other dimensions. In an embodiment, the diameter of a lead can change (e.g., become thinner, thicker, change in width) in response to forces and / or movement while avoiding fracture, displacement, migration, and / or dislodgement. For a fully implantable system (FIG. 20), in an embodiment, coiled or non-coiled leads (e.g., non-exhaustive lists includes conventional leads, closed leads, cylindrical leads, paddle leads, custom leads) can be surgically inserted or placed to mimic the musculoskeletal orientation (e.g., longitudinal muscle length, fascicle length, fiber length, pennation angle) of paraspinal muscles and other surrounding structures that largely connect at or near the posterior spinous process and largely terminate at or near the transverse spinous process (e.g., multifidus, iliocostalis, interspinales, rotator longus, rotator brevis, intertransversaii, and muscles of the erector spinae). In an embodiment, placement parallel or nearly parallel (e.g., 165-180 or 145- 165 or 130-160 or 120-150 degrees relative to the skin) to the structures of the musculoskeletal system (e.g., multifidus, iliocostalis, interspinales, rotator longus, rotator brevis, intertransversaii, and muscles of the erector spinae) reduces shearing forces, reduces the riskof lead or electrode fracture, and reduces unintentional movement or dislodgment, thus increasing longevity of the implanted lead and peripheral nerve stimulation system.

[0282] The systems, devices, methods, and instructions for use of systems, devices, and methods for electrode insertion are specifically chosen to withstand the dynamic shape changes experienced during muscle gearing. As a non-limiting example, the electrode insertion may circumvent or limit these forces by uniquely combining a curved introducer (e.g., place more lead under the skin to minimize dislodgement and place the lead through a path that avoids muscle planes to minimize shear stresses on the implanted electrode and lead) with a coiled lead (e.g., which coils and uncoils when forces (e.g., from surrounding tissue or from stimulation) are applied in the longitudinal direction of the lead), inserted using a cephalad- caudad needle trajectory of 120-150 degrees relative to the skin (FIG. 21) to mimic the musculoskeletal orientation (e.g., longitudinal muscle length, fascicle length, fiber length, pennation angle) of paraspinal muscles and other surrounding structures that largely connect at or near the posterior spinous process and largely terminate at or near the transverse spinous process (e.g., multifidus, iliocostalis, interspinales, rotator longus, rotator brevis, intertransversaii, and muscles of the erector spinae).

[0283] It is also to be appreciated that optimizing the orientation of the lead and / or electrodes to minimize the number of intersecting muscle planes, minimize the difference between the angle of the lead and the angle of the muscles it intersects, and / or reduce the muscles forces acting on the needle and / or electrode lead during movement could introduce new challenges. The present system, device, method, and instructions for use of systems, devices, and methods teach that the amount of lead under the skin, the ease of educating physicians on the method for placement, the capability of a physician to consistently achieve the desired approach, the safety of the placement technique, and the selection of the location of the lead insertion / exit site and bandaging on the patient, listed here as non-limiting examples,may influence the appropriate orientation of the lead and / or electrode and could require that the orientation that minimizes the number of intersecting muscle planes, minimizes the difference between the angle of the lead and the angle of the muscles it intersects, and / or reduces the muscles forces acting on the needle and / or electrode lead during movement not be used, but instead the optimal orientation that satisfies the majority, plurality, or most conditions be used, thus maximizing the effectiveness of the system (e.g., pain relief) and minimizing the potential for treatment interruptions (e.g., lead dislodgement, lead migration, lead fracture,) or sub-therapeutic treatment (e.g., due to patient discomfort or poor compliance).

[0284] Each component of the musculoskeletal system introduces a challenge or consideration that may differ depending on the target peripheral nerve, surrounding structures, or location on the body. However, in a non-limiting example, circumventing the challenges created by the complex musculoskeletal system creates new or additional challenges for the patient, for the physician, and / or for the placement or utilization of the stimulation device. As an example, to target a peripheral nerve at the lumbar spinal level L5, previous systems and methods have described percutaneously placing a lead via a posterior to anterior approach with an insertion approximately 90 degrees relative to the skin surface, thus crossing through multiple muscle planes at oblique angles relative to the orientation of the muscles such that repetitive contraction of the muscles (e.g., during normal movement and / or caused by stimulation of the nerve innervating the muscles) produces undesired shear forces on the lead. Outputs from a musculoskeletal model using the present invention describe placing the lead from caudad-cephalad (inferosuperior) at an angle with a 15-60-degree rotation in the frontal plane from mediolateral, thus mimicking the angle or alignment of muscle plane(s) of the paraspinal muscles. However, in this non-limiting example, while this caudad-cephalad (inferosuperior) approach may reduce or mitigate muscle shear forces, thus circumventing one challenge created by the complex musculoskeletal system, it would introduce sanitation andcomfort concerns for the patient from the resultant lead exit site being near the buttock and the bandage location being below the waistline on curved skin (e.g., increasing risk for percutaneous lead infection and increasing likelihood for discomfort from sitting on the exit site, and / or poor bandage adhesion). For each nerve target and associated region of the spine being treated, the present system and method teaches the unique balance that optimizes the placement of the electrode in a location that generates a desired neural response with the musculoskeletal impediments for placing the electrode in a targeted location, the interactions between the stimulation system and the complex movement of the musculoskeletal system, the considerations for the interaction between the patient and the system, and the considerations for the interaction between the physician and the system towards avoiding treatment interruption (e.g., lead migration, lead dislodgement, lead fracture), maximizing the likelihood of completing treatment, and maximizing the likelihood of significant and sustained pain relief.

[0285] In an embodiment, a shallower angle (e.g., 15-60 degrees or 120-180 degrees) or an acute angle or more acute angle (or in some cases an obtuse or more obtuse angle) results in a greater length of lead under the skin and may reduce the risk of lead or electrode dislodgement. In an embodiment, a cephalad-caudad (superoinferior) lead orientation of 120- 165 degrees mathematically places more lead under the skin than a perpendicular orientation or an orientation that is between 60 and 120 degrees relative to the skin. In an embodiment, an angled lead placement trajectory avoids causing undue discomfort to the patient. As an example, an angled lead placement trajectory avoids an area sensitive to allodynia whereas a perpendicular approach directly traverses an area sensitive to allodynia. In an embodiment, if a patient had pain and allodynia centered around lumbar level L2, the system and method would target the medial branch of the dorsal ramus at or near lumbar level L2, but the lead would be placed superoinferiorly (e.g., from superior to inferior, or cephalad to caudad), thus placing the lead and electrode along the path of the muscle planes and avoiding placing the needle throughthe region with allodynia. In an embodiment, an angled lead placement trajectory avoids off- target stimulation. As an example, an angled trajectory that is in line, parallel, or most parallel with muscle planes avoid stimulation of nerves innervating subcutaneous tissues.

[0286] The placement of lead and / or electrodes must take into account the safety considerations for the patient. As an example, during placement, the physician must avoid arteries, vessels, or entering the epidural space. As such, techniques that actively avoid or limit the likelihood of the physician coming into contact or being near arteries, vessels, or entering the epidural space should be preferred. As an example, if the nerve target was the medial branch of the dorsal ramus at the lumbar level, a needle trajectory that is inferosuperior, if advanced past the nerve (e.g., deeper than the target), has the potential to enter the epidural space and elicit severe damage. Alternatively, a needle trajectory that is superoinferior, if advanced past the nerve (e.g., deeper than the target), would come in contact with the vertebral lamina, thus stopping the needle and protecting the patient from damage. Thus, the present system, device, method, and instructions for use of systems, devices, and methods teach that, in a non-limiting example, at the lumbar level of the spine, one consideration to incorporate into the planning of a lead placement to maximize efficacy (e.g., pain relief) for a patient with lumbar spine pain, is that a cephalad-caudad approach is preferred to a caudad-cephalad approach due to the safety provided by the vertebral lamina, which protects from accidental entry of a needle into the epidural space.

[0287] For percutaneous systems, the placement of the lead and / or electrodes must take into account the bandaging location for the lead exit site. As an example, if the nerve target was the medial branch of the dorsal ramus at lumbar level L5, a needle trajectory that is caudad- cephalad (inferosuperior) places the lead exit site and bandaging lower (inferior or caudad) on the back towards the buttocks, thus creating sanitation concerns, increasing discomfort for the patient, reducing the likelihood of treatment compliance and successful therapy. Alternatively,a needle trajectory that is superioinferior places the lead exit site and bandaging (superior or cephalic) on the back towards the thoracic region and away from the buttocks (i.e., inter-gluteal cleft), thus minimizing or reducing sanitation concerns, placing the bandage in a more accessible area, and increasing the likelihood of treatment compliance and successful therapy (FIG. 22). As another example, if the nerve target was the medial branch of the dorsal ramus at cervical level C6, a needle trajectory that is superioinferior places the lead exit site and bandaging higher on the neck into the patient’s hairline, thus increasing discomfort for the patient and reducing the likelihood of treatment compliance and successful therapy. Alternatively, a needle trajectory that is caudad-cephalad (inferosuperior) places the lead exit site and bandaging lower on the neck, thus avoiding the patient’s hairline, and increasing the likelihood of treatment compliance and successful therapy (FIG. 23). Thus, the present system, device, method, and instructions for use of systems, devices, and methods teaches that, in a non-limiting example, at the lumbar level of the spine, one consideration to incorporate into the planning of a lead placement to maximize efficacy (e.g., pain relief) for a patient with lumbar spine pain, is that a cephalad-caudad approach is preferred to a caudad-cephalad approach due to the increased comfort and sanitation accomplished by placing the insertion point and corresponding bandage away from the buttocks. However, the present system, device, method, and instructions for use of systems, devices, and methods also teaches that, in a non-limiting example, at the cervical level of the spine, one consideration to incorporate into the planning of a lead placement to maximize efficacy (e.g., pain relief) for a patient with cervical spine pain, is that a caudad-cephalad approach is preferred to a cephalad-caudad approach due to the difficulty and chances for unsanitary conditions associated with bandaging over hair on the head, while hair on the neck and back pose no problem to readily available bandages.

[0288] In an embodiment, the present invention includes at least one lead that is designed to reversibly change lead-shape in one or more dimensions in response to forces applied on the lead and the at least one lead is configured for insertion into a portion of the body such that the longitudinal axis of the lead is sufficiently aligned with the direction of net force and / or movement by the musculoskeletal system in the implanted bodily region to avoid lead fracture or migration to prevent interruption of therapeutic delivery of electrical stimulation to a nerve. In a preferred embodiment, alignment of the lead is sufficient when it is parallel or nearly parallel (e.g., -30°, -29°, -28°, -27°, -26°, -25°, -24°, -23°, -22°, -21°, -20°,0°, 1°, 2°, 3°, 4°, 5°, 6°, 7°, 8°, 9°, 10°, 11°, 12°, 13°, 14°, 15°, 16°, 17°, 18°, 19°, 20°, 21°,22°, 23°, 24°, 25°, 26°, 27°, 28°, 29°, 30°) or partially parallel (e.g., 0-15%, 0-30%, 0-50%,15-30%, 30-50%) with the direction of net force and / or movement. In another embodiment, alignment of the lead is sufficient when it is parallel or nearly parallel (e.g., 0-15°, 0-30°, 0- 45°, 15-45°, 15-60°, 0-60°, 0-90°) or partially parallel (e.g., 0-15%, 0-30%, 0-50%, 15-30%, 30-50%, 0-75%) with the direction of net force and / or movement. Once the alignment has been determined or identified, it may be described, provided, and / or instructed to the user (e.g., the physician, clinician, provider, etc.) in terms of identifiable landmarks, directions, and / or orientations (e.g., including a combination of an angle or a shallow angle or an acute angle relative to the skin or skin surface, an angle relative to a landmark or body part, such as the head (e.g., cephalad, cranial, superior, etc.), anatomical direction such as medial or lateral, and / or an angle toward or away from a structure, such that the invention avoids the need for the physician or clinician user to have knowledge of force vectors, net force, vectors or directions of muscle movements that may be produced by the invention (e.g., during and / or by stimulation) and / or during the on and / or off periods of stimulation and / or the relative stresses and / or forces placed or generated, received, and / or absorbed by the invention’s system(s)and / or component(s). In another embodiment, alignment of the lead is sufficient when it enables change in lead shape in one of more directions while avoiding lead fracture or migration. In another embodiment, alignment of the lead is sufficient when it enables elastic shape change (i.e., movement with the musculoskeletal system, while returning to initial shape after the movement) while avoiding lead fracture or migration. In another embodiment, alignment of the lead is sufficient such that the lead is compliant with the movement of the musculoskeletal system while avoiding lead fracture and migration. In an embodiment, a lead has at least one portion that is compliant (i.e., moves with the musculoskeletal system) and at least one portion that is non-compliant (i.e., does not move with the musculoskeletal system). In an embodiment, a lead with at least one portion that is compliant (i.e., moves with the musculoskeletal system or with muscle as muscle moves) avoids lead fracture or migration during musculoskeletal movement that is caused during normal activities or as a result of stimulation. In an embodiment, a lead with at least one portion that is compliant (i.e., moves with the musculoskeletal system or with muscle as muscle moves) and at least one portion that is elastic (i.e., able to be stretched and return to its original shape), with the compliant portion and the elastic portion being the same or different portions of the lead, enables therapeutic stimulation of the desired target nerve while avoiding lead fracture or migration. In an embodiment, a lead with at least one portion that is compliant (i.e., moves with the musculoskeletal system or with muscle as muscle moves) and at least one portion that is elastic (i.e., able to be stretched and return to its original shape), with the compliant portion and the elastic portion being the same or different portions of the lead, is oriented such that the complaint and / or elastic portion of the lead is aligned with the direction of net force and movement by the musculoskeletal system in the implanted bodily region to avoid lead fracture or migration and prevent interruption of therapeutic delivery of electrical stimulation to a nerve. In an embodiment, a lead with at least one portion that is compliant (i.e., moves with themusculoskeletal system or with muscle as muscle moves) and at least one portion that is elastic (i.e., able to be stretched and return to its original shape), with the compliant portion and the elastic portion being the same or different portions of the lead, is oriented such that the portion of the lead that is not complaint and / or not elastic portion is aligned with the direction of net force and movement by the musculoskeletal system in the implanted bodily region and the portion of the lead that is compliant and / or elastic is not aligned with the direction of the net force and movement, thus minimizing the deleterious forces on the fragile portions on the lead (the portions that are not compliant and / or elastic) and subjecting the unavoidable forces to the portions of lead that are able to withstand greater force (the portions that are compliant and / or elastic), thus avoiding lead fracture or migration. As shown in FIG. 24, sufficiently orienting the lead to satisfy the plurality or majority of conditions, thus maximizing the effectiveness of the system (e.g., pain relief) and minimizing the potential for treatment interruptions (e.g., lead dislodgement, lead migration, lead fracture) or sub -therapeutic treatment (e.g., due to patient discomfort or poor compliance) enables the present system and method to modulate central neural processing to reduce the perception of pain. As shown in FIG. 25, the same non- exhaustive list of considerations used in FIG. 24 may lead to different recommended approaches based on the region of the body.

[0289] In an embodiment to treat bilateral spine pain, patients are treated with two leads placed bilaterally targeting the same nerves on each side of the spine, and when two percutaneous leads are placed bilaterally, it is desirable to have the lead exit sites both under one bandage to minimize discomfort and potential for infection. In an embodiment, the target location of the electrode (e.g., the area a close but remote distance from the target nerve, 0.5- 1.5 cm from the target nerve (or 0.1-3 cm, 0.1-2 cm, 0.2-2cm, 0.2-3cm, and / or 0.3-3cm), approximately 1 cm from the target nerve) is approximately 2-5 cm (or 1-5 cm, 2-4 cm, 1-3 cm, 3-5 cm) from the midline, and thus two target locations bilaterally are approximately 4-10cm apart (or 2-10 cm, 4-8 cm, 2-6 cm, 6-10 cm). If such sites are approached from directly caudad or cephalad (i.e., with no medial-lateral direction), the exit sites of two bilaterally placed percutaneous leads are approximately 4-10 cm apart (or 2-10 cm, 4-8 cm, 2-6 cm, 6-10 cm). Thus, the present system, device, method, and instructions for use of systems, devices, and methods teach that one consideration to incorporate into planning the placement of leads for the treatment of spine pain is to avoid a lateral-medial approach in favor of a straight (no medial-lateral directionality) or slight medial-lateral approach in order to place both lead exit sites under one bandage of minimal size, which increases patient comfort and compliance, thereby increasing likelihood of a successful treatment (e.g., maximizing pain relief).

[0290] In an embodiment, the area of spine pain being treated is in the cervical spine (e.g., the targeting of the medial branch nerves at the level of C4-C7), and the vertebral arteries on the lateral sides of the articular pillar are vulnerable to puncture by a needle advancing in a lateral-medial direction and thus a lateral-medial approach for the placement of a lead should be avoided. Thus, the present system, device, method, and instructions for use of systems, devices, and methods teaches that one consideration to incorporate into planning of the placement, implantation, delivery, of a lead for the stimulation of nerves surrounding (nearby, close to) the cervical spine is the avoidance of the vertebral arteries.

[0291] In an embodiment, the area of spine pain being treated is in the cervical spine (e.g., the targeting of the medial branch nerves at the level of C4-C7), and crossing more mobile segments (i.e., vertebra) of the neck with the lead increases the likelihood of the lead migrating away from the target nerve. Data on the rate of migration of leads was collected from patients who received percutaneous lead with the distal tip over (posterior to) the C2 vertebra, with the entry sites ranging from over the C4 vertebra to the C7 vertebra, which showed that the rate of migration was highest when entry was over C7, next highest when entry was over C6, next highest when entry was over C5, and lowest when entry was over C4. Thus, the present methodteaches that one consideration to incorporate into planning of the placement, implantation, delivery, of a lead for the stimulation of nerves surrounding (nearby, close to) the cervical spine is to balance the tradeoff between having enough lead under the skin to allow for securement via tissue ingrowth around the lead and not so much lead under the skin such that the mobility of the surrounding tissue (e.g., the mobile neck) causes migration.

[0292] In addition to muscle, placement of the system may be impeded, made more difficult, obstructed, or otherwise challenged by other musculoskeletal components that include, but are not limited to, layers of muscles, bone, vertebrae, tendons, ligaments, fascia, nerves, vessels, and aponeuroses. As an example, placement of the lead(s) and / or electrode(s) must circumvent bony structures (e.g., vertebrae) that act as barriers. As an example, as shown in FIG. 26 a physician may want to percutaneously place a lead and electrode at a shallow angle or acute angle in the lumbar region, with a lateromedial and cephalad-caudad trajectory, though such an angle may be obstructed or cause the needle to be deflected by the facet joint. As an example, the present invention teaches that a needle trajectory that is parallel to the spine or is mediolateral avoids the transverse spinous process and facet joints and enables effect lead / or electrode placement. As an example, the present invention utilizes a curved needle to navigate bony and / or other musculoskeletal structures (e.g., fascia) to enable effective lead and / or electrode placement, and avoid deflection or distortion by those structures.

[0293] In a preferred embodiment, optimizing the orientation of the lead minimizes treatment interruptions (e.g., lead dislodgement, lead migration, lead fracture) and avoids patient discomfort (e.g., due to spasms, uncomfortable stimulation intensity, or location of electrode) and poor compliance. As an example, avoiding lead migration by optimizing lead orientation prevents the deleterious effects of migration, that include but are not limited to uncomfortable stimulation, off-target stimulation, muscle spasms, painful sensations from stimulation, and increased or worsening of pain. As an example, avoiding lead dislodgementor lead fracture by optimizing lead orientation prevents the patient from undergoing a repeat procedure and / or prevents the patient from having a lead fragment or retained lead, this increasing the rate of lead survival for the entirety of the prescribed treatment period (FIG. 27).

[0294] In an embodiment, the present system modulates central neural processing (e.g., in the CNS, such as the spinal cord, brain, and / or other central neural processing centers) to reduce the perception of pain, and this modulation of central neural processing is achieved without requiring blocking of transmission of neural pain signals from periphery (e.g., through peripheral and / or spinal nerves and distal branches) to and / or from the central nervous system.

[0295] In an embodiment, the present system, device, method, and instructions for use of systems, devices, and methods activate peripheral spinal nerves (e.g., afferent, efferent, or mixed nerves as they exit or after they exit the spinal canal or foramen) or other peripheral nerves (e.g., nerve trunks or branches) of the dorsal rami, the ventral rami, and / or in or around the paravertebral space or in other locations to generate neurally encoded signals in the afferent fiber(s), such that the neurally encoded signals modulates processing of pain, and while the location of the stimulation and the electrode are outside of the spinal cord and DRG, the present invention can cause, trigger, change, or perpetuate a cascade of events that ultimately modulate the processing of pain at one or more levels, including modulation of pain pathways and processing in the periphery, in the central nervous system (e.g., including the spinal cord and / or the brain), and / or in levels or centers in between (e.g., such as the DRG which is located between the portion of the peripheral nerve that is stimulated and the spinal cord). Sustained pain relief is critical to produce substantial impacts on a patient’s quality of life and improve function, and, in an embodiment, is accomplished by eliminating, modulating, blocking, diminishing, or attenuating the source of painful signals or the painful signals being transmitted by the peripheral nerves, and / or addressing problems in the pain processing (e.g., maladaptive, atypical, pathologic, or other changes, plasticity, or alterations in processing of pain and / orsignals that can lead to pain) at, in, within, or across centers, levels, or locations in the peripheral nervous system, in the DRG, and / or in the central nervous system (e.g., including the spinal cord and / or the brain) system that yield chronic pain. Thus, in an embodiment, the present system, device, method, and instructions for use of systems, devices, and methods include stimulating peripheral nerves to modulate pain processing in the central nervous systems (e.g., the spinal cord and / or the brain), peripheral nervous system, and / or DRG, etc. while also achieving the goal of being minimally invasive and avoids the need to be in, on, or near the DRG, the spinal cord, and / or the brain. The system is designed to produce modulation of central pain processing such that the perception of pain is reduced or eliminated, and this reduction or elimination of pain outlasts the duration of the stimulation of the peripheral nerve(s). Modulating or reconditioning central pain processing during the course of a stimulation treatment period requires that the implanted lead provide consistent, selective stimulation of target fibers in the target nerve(s), and the present invention enables such modulation or reconditioning by placing stimulating leads in or through one or more muscles using orientations, angles, or trajectories that are optimized to reduce the forces or combinations of forces (e.g., tensile, shear, compressive, and / or bending forces) on the lead to maintain lead positioning relative to the target nerve by preventing lead migration, dislodgement, and / or fracture.

[0296] The present system is designed to provide peripheral nerve stimulation to modulate the central pain processing. In one embodiment, the present system modulates, changes, restores, or reconditions central pain processing through the use of a self-anchoring electrode and / or lead that can be temporarily placed through a simple and / or minimally invasive percutaneous insertion (e.g., non-surgical placement, implantation, insertion, etc.), avoiding the need to permanently place an electrode or lead with surgery. It is to be appreciated that in other embodiments, the same effect and method is accomplished by more invasivemeans such as surgery (e.g., placement of lead in and through the epidural space or spinal canal), but this invention enables activation of peripheral nerves (e.g., branches of the dorsal rami or branches of the ventral rami or those located in or near the paravertebral space) to produce pain relief in a way that desirably avoids and / or does not require surgery or surgical placement in or near the paravertebral space. As a non-limiting example, stimulation of peripheral nerves with the present system can produce neural activation in a way that desirably generates (e.g., produce, activates, encodes) neural signals in afferent fibers (e.g., either directly or indirectly) in the desired target nerve(s) to produce changes in central processing of pain (e.g., in the central nervous system, such as the spinal cord, brain, and / or other central neural processing centers). As a non-limiting example, stimulation of peripheral nerves (e.g., one or more branches of the dorsal ramus, spinal nerve, terminal branches of one or more nerve(s) that innervate(s) one or more paraspinal muscles, etc.) with the present system, device, method, and instructions for use of systems, devices, and methods can produce neural activation that contracts and / or relaxes muscle(s) comfortably and repeatedly (e.g., cyclically, intermittently, and / or regularly) to generate (e.g., produce, propagate) desirable neural signals in afferent fibers in a nerve that produce comfortable sensations and pain relief and / or changes in central processing of pain (e.g., in the central nervous system (CNS), such as the spinal cord, brain, and / or other central neural processing centers). The present invention provides a method of activation of nerves that enables / causes / promotes / creates changes in central nervous system processing in such a way that pain relief can outlast the duration of therapy (e.g., on short term and / or long term). Modulation of central pain processing may be brought about by activation of paraspinal muscles using peripheral nerve stimulation. Central pain reconditioning can outlast stimulation of the nerves that produced contraction of the muscles on the short term (e.g., second, minutes and / or days) or long term (e.g., days, weeks, months and / or years) after stimulation stops being applied to nerves. This sustained therapeutic benefit offers anadvantage over the prior art and existing therapies, where continuous or long-term intermittent stimulation is required to produce pain relief and is unable to provide sustained, lasting benefit (e.g., relief of pain or improvement in function) after terminating the therapy. Furthermore, the present system and method may present an advantage over the prior art, as this long-lasting modulation of central pain processing may be accomplished with a system that is minimally- invasive (e.g., percutaneous electrode insertion), temporary (e.g., short-term therapy administered over a period of weeks), safe (e.g., coiled lead design has negligible risk of infection or device-related adverse events) and reliable (e.g., self-anchoring lead prevents lead migration, ensuring comfortable, uninterrupted therapy). As a further example, the present system and method may enable a short-term therapy (e.g., a temporary percutaneous system using a percutaneous lead coupled to an external stimulator) to provide long-term pain relief (e.g., by modulation of central pain processing). In an embodiment, the present system and method may present an advantage over the prior art, as the long-lasting modulation of central pain processing may be accomplished with a system that is permanently implanted but requires less frequent stimulation than the systems of prior art, thereby allowing the system to last longer on a given battery charge.

[0297] Contraction of muscles may be evoked using electrical stimulation in many possible ways. Electrical stimulation may be used to activate motor axons in the nerve (e.g., group A neural fibers at the dorsal ramus or peripheral nerves), at motor points of muscles, where motor axons enter a muscle, or activate the muscle directly (e.g., without activation of the motor axons). However, threshold stimulation intensities for activation of motor axons may typically be lower than intensities required for direct activation of muscle. Electrical stimulation may also be used to stimulate other parts of the body to cause a reflex response that activates the target muscle. Stimulation may also be used to activate one or more muscles by stimulation of the dorsal ramus of spinal nerve, ventral ramus of spinal nerve, dorsal rootganglion, spinal nerve, and / or the spinal cord. Stimulation may also be used to activate nerves that produce activation of muscles that is not in the neck (e.g., a shoulder muscle, a back muscle etc.) that may cause passive movement (e.g., stretching, compression, torsion) of a neck muscle. In a preferred embodiment, the selection of peripheral nerves as the stimulation target is an improvement over the current methods of targeting muscles and / or motor points in the muscles with stimulation, as the present invention may produce widespread motor activation in addition to simplifying the procedure for placement of electrodes and / or leads by minimizing number of leads required to produce activation of paraspinal muscles in the region of pain and avoiding need to reposition needles and / or electrodes multiple times.

[0298] As a non-limiting example, this system, device, method, and instructions for use of systems, devices, and methods may enable the activation of peripheral nerves and / or their branches in or near the paravertebral space to generate comfortable sensations (e.g., paresthesia, muscle activation) and / or relief of pain (e.g., suppression, distraction, or absence of pain) in a desired area of the body (e.g., painful region). Neural structures that may be targeted (e.g., activated, stimulated) with stimulation in or around the paravertebral space include the spinal nerves, spinal roots, the dorsal and ventral rami, the rami communicantes, the sympathetic chain, dorsal root ganglion, or other nearby nerve trunks or branches. As another non-limiting example, this system, device, method, and instructions for use of systems, devices, and methods may enable the activation of peripheral nerves and / or their branches in the spinal region but outside the paravertebral space to generate comfortable sensations (eg.., paresthesia, muscle activation) and / or relief of pain (e.g., suppression, distraction, or absence of pain) in a desired area of the body (e.g., painful region). Neural structures that may be targeted (e.g., activated, stimulated) with stimulation outside the paravertebral space include but are not limited to medial, lateral, or other branches of the dorsal or ventral rami, gluteal nerve and branches, the cluneal nerve and branches, the superior cluneal nerve and branches,middle cluneal nerves and branches, occipital nerves and branches, or any other suitable peripheral nerve with sensory and / or motor innervation of spinal structures. Activation of these nerves may be widespread, limited, or desirably controlled to the appropriate and / or therapeutic regions or levels most effective in generating neurally encoded signals (e.g., in afferent nerve fibers) to evoke changes in central processing of pain.

[0299] By targeting the peripheral nerves (e.g., spinal nerve, dorsal ramus, distal branches, etc.) with this approach, stimulation may produce (e.g., generate, activate, trigger) widespread and / or controlled neural activity in a desired area to generate an increased amount (e.g., number, intensity, duration, etc.) of afferent nerve signaling that may modulate central pain processing, avoiding the need to place multiple electrodes and / or leads to relieve pain in the desired bodily region. Stimulation may be used to generate neural signals (e.g., biomimetic, physiologically encoded information) from or to local (e.g., nearby) or distal structures (e.g., portions of the back, neck, trunk, or extremities). The ability to customize the selection of particular peripheral nerves as the stimulation target and place leads to optimize the forces (e.g., tensile, shear, compressive, bending forces, etc.) is a significant improvement over the current methods of targeting the spinal canal (e.g., spinal cord, dorsal root ganglia, etc.) with stimulation, as the present approach may produce tailored pain relief through the activation of selected nerve targets while preventing lead migration, dislodgement and fracture for the duration of a defined stimulation treatment period, in addition to simplifying the procedure for placement of electrodes and / or leads (e.g., by minimizing number of electrodes or leads required, avoiding need to reposition needles and / or electrodes multiple times, and avoiding invasive or surgical placement (e.g., in or through the epidural space).

[0300] The present system, device, method, and instructions for use of systems, devices, and methods may produce activation of nerves that may reduce pain or the perception of pain without directly strengthening or requiring strengthening of paraspinal muscles.Stimulation of nerves may produce activation of neural pathways that influence the perception, processing, and / or generation of pain signals, and the goal of stimulation is to activate those pathways to restore normal or improved pain processing. The present system and method may enable the modulation of central pain processing via the stimulation of peripheral nerves and activation of paraspinal muscles, however this generation of afferent signals that may modulate central processing does not require that muscles be strengthened. In contrast to other therapies, the strengthening, rehabilitation, and / or stabilization of paraspinal muscles (e.g., change in the size, shape, composition, or endurance of muscle) is not required for pain relief, as stimulation to activate muscle fibers generates neurally encoded afferent signals, which may modulate central pain processing, irrespective of the strength of muscles. Therefore, the present system and method may enable the stimulation of nerve fiber(s) in peripheral nerves producing changes in central pain processing (e.g., brain, spinal cord, and / or other central neural processing centers) to modulate the perception of pain, without requiring changes in the muscles themselves. In another embodiment, pain may be reduced without providing mechanical strengthening, and although mechanical strengthening may occur, it is not required as part of the present system and method. As an additional example, the present system and method may enable the modulation of central pain processing via the stimulation of peripheral nerves and peripheral nerves that innervate paraspinal muscles, and the modulation of pain processing and / or modulation of pain (e.g., conveyance of pain relief) may be provided prior to or without requiring functional improvement (e.g., modulation of pain processing and / or pain relief may be provided in a patient with spine pain prior to or without providing functional improvement, changes in muscle strength, stability, flexibility, and / or other mechanical or functional outcomes). While the modulation of central pain processing may occur without direct (e.g., stimulation-evoked) strengthening of muscles, such changes may occur, but they are not required for the present system and method to modulate pain processing. As an example,the present system and method may modulate neural processing without altering function. In another embodiment, the present system may reduce pain through modulation of central sensitization, while also improving (e.g., increasing, restoring) healthy descending (e.g., efferent) neural signaling, which further enables improvements in pain and function through the restoration of healthy peripheral tissue (e.g., nerve, muscle) and function (e.g., healthy nerve signaling).

[0301] Furthermore, this present system, device, method, and instructions for use of systems, devices, and methods is designed to create pain relief by stimulation of peripheral nerves and activation of central pain processing via generation of afferent signals without requiring stabilization of the spine, musculature, or connective tissues (e.g., tendons, ligaments, etc.). Stimulation and activation of musculature may generate neurally encoded signals that relieve pain and / or modulate pain signal processing unrelated to the stability or status of bones, musculature, or connective tissue. Thus, the present system and method presents an advantage over the prior art; as this system enables activation of peripheral nerves and paraspinal muscles that generate afferent signals to modulate central pain processing, enabling reductions in pain prior to or without mechanical stabilization. Further, this system provides pain relief through changes in central pain processing without requiring targeted or regenerative changes in the stability of the spine, musculature, or connective tissue. In another embodiment, pain can be reduced without providing mechanical stability, and, although mechanical stability may occur, it is not required as part of the present system and method.

[0302] Beyond pain relief, the present invention (e.g., including the system(s), device(s), method(s), and methods of using and / or delivering the system, devices, and / or method(s)) may improve the physical functioning of the patient without directly strengthening or requiring strengthening of paraspinal muscles. Patients with chronic spine pain often reduce their movement, activity, functionality, or ability to complete activities of daily living due toguarding behaviors (e.g., fear or apprehension of pain during such movements), thus resulting in decreased physical function. Over time reduced activity decreases the neuronal connections responsible for creating movement decrease, leading to further reductions in physical function. Stimulation and activation of muscles may generate neurally encoded signals that increase the neuronal connections responsible for creating movement, leading to improved physical function without directly strengthening or requiring strengthening of paraspinal muscles. The improvement of physical function may also or further occur through the relief of pain, which reduces the fear or apprehension of movement (e.g., kinesiophobia). In one non-limiting example, a patient with back pain may avoid walking and standing for long periods of time due to their pain, and when stimulation treatment is started, their physical functioning may improve before or after pain decreases. The present invention provides a method for improving physical functioning in patients with chronic pain through the alteration of central processing of sensory inputs from the region of pain and strengthening (increasing, altering, improving) of neuronal connections between the central nervous system and the peripheral nerves innervating the region of pain. Once these connections have been increased, the improvements in physical function can outlast the duration of stimulation treatment or therapy (e.g., short-term on the order of seconds / minutes / hours or long-term on the order of days / months / years). The present system provides a method of stimulation of nerves or activation of nerves that enables changes in the central nervous system processing in such a way that both pain and physical function improve without strengthening and without requiring the strengthening of muscles in the region of pain. The present system provides a method of stimulation of nerves or activation of nerves that innervate the region surrounding the spine (e.g., neck, upper back, middle back, low back) that enables changes in the central nervous system processing in such a way that both pain and physical function improve without strengthening and without requiring the strengthening of the paraspinal muscles. When physical functioning improves, a patient may become moreactive and thus increase the frequency and amplitude of forces in the paraspinal muscles that act on the lead. The present invention teaches that by aligning the lead with the direction of the muscle fibers, the lead will move with the muscle and avoid migration and fracture that may interrupt treatment.

[0303] In an embodiment, the present system provides a method of stimulation of nerves or activation of nerves that enables changes in central nervous system processing in such a way that can outlast the duration of stimulation treatment or therapy (e.g., on short term and / or long term). Modulation of central spinal processing brought about by the stimulation of nerves or activation of nerves, which may be activated, produced, driven, or generated by peripheral nerve stimulation and may outlast stimulation of the nerves on the short term (e.g., second, minutes and / or days) or long term (e.g., days, weeks, months and / or years) after stimulation stops being applied to nerves. This sustained therapeutic benefit offers an advantage over the prior art and existing therapies (e.g., implanted systems), where continuous or long-term intermittent stimulation is required to produce pain relief, and / or sustained, lasting benefit (e.g., relief of pain) cannot be achieved after terminating the therapy. Prior art and existing therapies (e.g., implanted systems) that seek to block (e.g., overshadow, coverup, stop, disrupt, disturb) pain signals are therefore limited in their long-term benefits (e.g., relief of pain) without long-term use (i.e., stimulation) of the device. The present system overcomes limitations of blocking neural signals (e.g., loss of sensory or motor function, loss of sensation, loss of proprioceptive control or feedback) by instead modulating pain processing in the central nervous system during the treatment period (e.g., days, weeks, months) to provide long term benefits (e.g., relief of pain) after the device is removed. Furthermore, the present system may present an advantage of the prior art, as this long-lasting modulation of central pain processing may be accomplished with a system that is minimally-invasive (e.g., percutaneous electrode insertion), temporary (e.g., short-term therapy administered over a period of weeks), safe (e.g.,coiled lead design has negligible risk of infection or device-related adverse events), reliable (e.g., self-anchoring lead implanted along an angle, path, and / or trajectory that optimizes the forces (e.g., tensile, shear, compressive, or bending forces) on the lead to prevent lead migration or dislodgement, ensuring comfortable, uninterrupted therapy) and enables customized placement of one or more electrodes to generate stimulation sensations resulting in pain relief in the desired area. As a further example, the present invention provides pain relief that may outlast the stimulation period, enabling use as a short-term therapy (e.g., a temporary percutaneous system using a percutaneous lead coupled to an external stimulator) to provide long-term pain relief (e.g., by modulation of central pain processing).

[0304] In another embodiment, the present system may be fully implanted and connected to a permanently implanted stimulator to provide continuous pain relief through this same method. The permanently implanted system may also be used to provide long-term pain relief as a follow-on or subsequent therapy for patients. In an embodiment in which the system is fully implanted and connected to a permanently implanted stimulator, the present invention provides benefit over prior art by increasing reliability (e.g., self-anchoring lead implanted along an angle, path, and / or trajectory that optimizes the forces (e.g., tensile, shear, compressive, or bending forces) on the lead to prevent lead migration or dislodgement, ensuring comfortable, uninterrupted therapy).

[0305] Unlike some existing therapies and prior art for electrical stimulation or neurostimulation (e.g., PNS, DRGS, SCS, TENS, etc.), which seek to continuously block (e.g., stop, cover up, disrupt, disturb), modulate, or attenuate neural signals responsible for pain, the present system can enable effective long-term treatment of the pain (e.g., the central processing of neural inputs may alter or modulate the pain processing and / or perception of pain signals) without blocking neural signals and without requiring continuous stimulation long-term to provide long-term pain relief. Furthermore, in one embodiment, this system may be used toenable pain relief resulting from various causes of pain, via activation of peripheral nerves, nerve branches, or nerve trunks and the modulation of central pain processing.

[0306] As a non-limiting example, the present invention employs nerve stimulation to modify, augment, transform, or regulate physiological processes of neural signal encoding, which can modulate pain processing, without use of and avoiding signal transmission blockade (e.g., neuroablative procedures or surgery, which permanently damage nerves, or neurostimulation systems which seek to block transmission of signals to central processing centers). The system may directly address the manifestation of pain at the central neural processing level, unlike other systems, which focus on modifying or blocking incoming signals from the periphery. The present system may modulate central neural processing without nerve blocking because the invention enables reduction and / or elimination of pain via modulation of central neural processing (i.e., nerve block is not required and the present invention desirably avoids nerve block). The present invention provides relief without nerve block and the present invention provides relief while avoiding nerve block.

[0307] The stimulator may include an electrical stimulation pulse generator. Control of the electrical stimulation device (e.g., the pulse generator) and stimulation parameters may be provided by one or more external controllers. Alternatively, a controller may be integrated with the external electrical stimulation device. In the embodiment wherein stimulation is applied using an implanted pulse generator, an external controller (i.e., clinical programmer) may be a remote unit that uses RF (Radio Frequency) wireless telemetry communications (rather than an inductively coupled telemetry) to control the pulse generator. The electrical stimulation device may use passive charge recovery to generate the stimulation waveform, regulated voltage (e.g., 1 mV to 15 mV, 0.5 mV to 30 mV, 10 mV to 20 V), and / or regulated current (e.g., about 0.2 mA to 50 mA, 1 mA to 30 mA, 0.5 mA to 50 mA, 10 mA to about 50 mA). Passive charge recovery may be one method of generating a biphasic, charge-balanced pulseI l las desired for tissue stimulation without severe side effects due to a DC component of the current.

[0308] The pulse generator may include a lightweight, durable housing that may be fabricated from a suitable plastic or the like. In some embodiments, the case may include a clip or snaps that allows the pulse generator to be releasably connected to a patient's belt, other clothing, or any other convenient location. The case may also include a releasable battery access cover. Other means of securing the stimulator may be used that allow the stimulator to be secured to the patient’s skin without and / or under clothing (e.g., adhesive, magnet, etc.).

[0309] For output of data to a patient or clinician operating the stimulation system, a visual display may be provided. The display may be by a liquid crystal display, but any other suitable display may alternatively be used. An audio output device, such as a beeper may also be provided. Alternatively, data may be conveyed to the user in other ways (e.g., tactile, flashing LEDs).

[0310] For user control, adjustment, and selection of operational parameters, the stimulation pulse generator may include a mechanism or device for input of data. The pulse generator may include an increment switch, a decrement switch, and a select or “enter” switch. The increment and decrement switches may also be used to cycle through operational modes or patterns and stimulation parameters displayed on the display, while the select switch may be used to select a particular displayed operational pattern or stimulation parameter. The select switch may also act as a power on / off toggle switch.

[0311] In a preferred embodiment, for output of electrical stimulation pulse train signals, the pulse train generator includes an external connection socket that may mate with a connector of an electrode cable assembly to interconnect the pulse generator with a plurality of electrodes, such as through use of percutaneous electrode leads. In an embodiment, the cable assembly connected to the socket includes a second connector such as on a distal end that maymate with a connector attached to the proximal end of each of the percutaneous stimulation electrode leads and a reference electrode lead. Alternatively, in an embodiment, the pulse generator transmits signals without a physical connection to the electrode (e.g., radio-frequency coupling, passive polarization of electrode) or may be housed within a single unit along with the electrode.

[0312] The system may use multiple types of electrodes and leads to apply stimulation to nerve(s). In an embodiment the lead(s) may include a temporary or permanently implanted helically coiled, open-coil, or closed-coil fine wire electrode (FIG. 28). In other embodiments, the leads may include any other type of electrode and lead, such as a straight or uncoiled fine wire, paddle electrode, needle electrode, cylindrical electrode, intramuscular electrode, general -purpose electrode, skin surface, cutaneous, transcutaneous, or any other appropriate type of electrode (whether known today or developed thereafter), placed or inserted via a needle introducer, percutaneously, non-invasively, and / or surgically implanted with one or more open incisions. In one embodiment, a coiled fine-wire electrode lead (or multiple electrode leads) is placed using a needle introducer and, once proper placement of the electrode is confirmed (i.e., in its appropriate operative position remote from the target nerve such that stimulation produces comfortable sensations focally in the region(s) of pain), and the needle introducer may be withdrawn, leaving the lead(s) and / or electrode(s) in place. Stimulation may also be applied through a penetrating electrode, such as an electrode array comprised of any number (e.g., one or more) of needle-like electrodes that may be inserted into the target site. In both cases, the lead may be placed using a needle-like introducer, allowing the lead(s) and electrode placement to be minimally invasive. In a representative embodiment, the lead(s) includes a thin, flexible component made of a metal and / or polymer material. As an example, by "thin," it is contemplated that the lead(s) is not greater than about 0.75 mm (0.030 inch) in diameter.However, the present teachings are not limited to such dimensions. Any appropriate electrode and lead may be utilized without departing from the present teachings.

[0313] In a preferred embodiment, the lead is elastic (e.g., changes shape reversibly, absorbs and releases energy) in one or more dimensions of the lead in response to forces applied on the lead such that the electrode stays in place (e.g., does not move or moves minimally such that the therapeutic effects of stimulation are not lost, diminished, or changed) relative to the target nerve. In an embodiment, the elastic limit of the lead (the length at which once stretched it cannot return to its initial shape) is more than or at least as great as the length that the tissue surrounding the lead can maximally change shape, such as due to muscle elongation or bulging. A lead designed to deform (e.g., change in shape, size, or position due to the application of forces or displacements, including but not limited to shortening, lengthening, elongation, translation, bending, twisting, compression, and / or stretching) in one or more dimension in response to forces applied on the lead from the surrounding tissue (e.g., from muscles contracting, stretching, twisting) and returns to original shape avoids interruption of therapeutic delivery of electrical stimulation to a target nerve by maintaining the location of the electrode relative to the nerve. In one embodiment, the elasticity (property of reversibly changing shape) of the lead is created through coiling of the lead such that the lead body acts as a spring. In another embodiment, the elasticity of the lead is due to stretchy or elastic polymer and the lead body may or may not be coiled. The present invention teaches that avoiding lead displacement to prevent interruption of therapeutic delivery of electrical stimulation is accomplished by aligning the longitudinal axis of an elastic lead with the direction of the greatest force and / or movement (stretch, compression, twist, bend) of the surrounding tissue.

[0314] In an embodiment, the lead(s) also include one or more coiled metal wires with an open or flexible elastomer core. As an example, the wire is insulated, e.g., with a biocompatible polymer film, such as polyfluorocarbon, polyimide, or parylene, or otherappropriate insulating material. In the example, the lead is electrically insulated everywhere except at, for example, one (monopolar), or two (bipolar), or three (tripolar), or more than three (e.g., 4, 5, 6, 8, 10, 12, 16, 32) conduction locations near its distal tip of the same or different sizes, lengths, and / or dimensions (e.g., 0.1mm, 0.2 mm, 0.3 mm, 0.5 mm, 1 mm, 3 mm, 5 mm, 7 mm, 10 mm, 15 mm, 20 mm, 1.0 cm, 0.2-1.5 cm, 0.1-3.0 cm, 1-10 cm in length) separated by non-conducting lengths of the same or different sizes and / or dimensions (e.g., 0.1mm, 0.2 mm, 0.3 mm, 0.5 mm, 1 mm, 3 mm, 5 mm, 7 mm, 10 mm, 15 mm, 20 mm, 1.0 cm, 0.2-1.5 cm, 0.1-3.0 cm, 1-10 cm in length). Each of the conduction locations may be connected to one or more conductors that may run the length of the lead(s) and extension cable or cables used to connect the lead to an external pulse generator / stimulator or a portion thereof. The conductor may provide electrical continuity from the conduction location through the lead to an external pulse generator or stimulator. In an embodiment, the lead(s) may exit through the skin and connect with one or more external electrical stimulation devices using cabling, connectors, and / or other components, features, and specifications. Further, the lead(s) may be connected as needed to internal and external coils for RF (Radio Frequency) wireless telemetry communications or an inductively coupled telemetry to control the stimulation device(s). The lead(s) may also be fully implanted and electrical stimulation may be delivered with a temporary or permanent fully implantable system, which could include a fully implantable lead and an implantable pulse generator (IPG) which may be controlled by external devices (such as a patient and / or clinician programmer and / or controller). The IPG may be powered by one or more internal sources, such as a rechargeable battery, energy banking, a primary cell or non- rechargeable battery, or other means. The implantable system may also be powered by external sources, including an external pulse transmitter, radiofrequency (RF) powering, induction, or other means. The electrode may also include an anchoring element at its distal tip and / or at one or more locations proximal (closer to the EPG or IPG) to one or more electrode contacts (e.g.,behind or closer to the EPG relative to the first electrode contact, behind or closer to the EPG relative to a second electrode contact, behind or closer to the EPG relative to one, more than one, or all electrode contacts, etc.). In the illustrated embodiments, the anchoring element may take the form of a simple barb or bend. The anchoring element may be sized and configured so that, when in contact with tissue, it takes purchase in tissue to resist dislodgement or migration of the electrode out of the correct location in the surrounding tissue. Desirably, the anchoring element may be prevented from fully engaging body tissue until after the electrode has been correctly located and deployed, and the anchor(s) may be designed to flex avoid damaging tissue during removal. However, it is to be appreciated that the anchor(s) may also be designed to be rigid (e.g., resist bending and / or flexing) to increase the securement of the lead in the tissue for such use with, in a non-limiting example, a long-term or permanently implanted lead that is not intended to be easily removed.

[0315] Inserting the lead(s) percutaneously allows the lead(s) to be placed quickly and easily. In one embodiment, the lead(s) may be placed percutaneously via an introducer needle to target one or more peripheral nerves without the use of incisions, surgical dissection, or open surgical techniques. The procedure may be performed without requiring regional or general anesthesia, enabling subjects to provide verbal feedback and / or confirmation of the location of stimulation-evoked sensations such that the lead(s) may be optimally placed to generate comfortable sensations in the region of pain. The introducer needle may be made from conductive, non-conductive, or a combination of conductive and non-conductive materials with the stimulating portion of the lead (e.g., the electrode) housed inside. This stimulating portion of the lead may protrude from the end of the needle itself to contact body tissue into which the lead is inserted. The distal end of the electrode may also protrude from the end of the needle in the same manner. The needle, lead, and / or electrode are then connected to an electrical stimulation device, such as an external pulse generator during / as a part of theintroducer / implantation process. Applying stimulating current through the electrode while it is housed within the introducer may provide a close approximation to the response that the electrode will provide when it is deployed at the location of the introducer needle because stimulation will be delivered through the same conductive portion of the electrode.

[0316] An exemplary embodiment of an electrode and percutaneous lead are shown in FIG. 28A. The electrode lead may be fabricated from a multi-strand (e.g., 7-strand, 19-strand, greater or fewer than 19 strands) stainless steel wire insulated with a biocompatible polymer. As an example, each individual wire strand may have a diameter of approximately 34 pm (or 1-10 pm, 10-20 pm, 20-30 pm, 30-40 pm, 40-50 pm, 50-60 pm, 60-70 pm, 70-80 pm, 80-90 pm, 90-100 pm, or greater than 100 pm) and the insulated multi-strand lead wire may have a diameter of approximately 250 pm (or 10-50 pm, 50-100 pm, 100-150 pm, 150-200 pm, 200- 250 pm, 250-300 pm, 300-400 pm, 400-500 pm, 500-600 pm, 600-700 pm, 700-800 pm, 800- 900 pm, 900-1000 pm, or greater than 1000 pm). It should be understood, however, that these dimensions are merely exemplary, and the present teachings are not limited to such. Any appropriately sized, shaped and configured electrode and percutaneous lead may be used. The insulated wire may be formed into a spiral or helix as has been found to accommodate high dynamic stress upon muscle flexion and extension, while simultaneously retaining low susceptibility to fatigue. As an example, the outer diameter of the helically formed electrode lead may be approximately 580 pm (or 100-250 pm, 250-500 pm, 500-750 pm, 750-1000 pm, or greater than 1000 pm) and it may be encased or filled with silicone or the like. Alternatively, the lead may have additional or fewer strands, may be made out of a different material (e.g., another metal, conducting polymer), may be insulated with another material, or may not be insulated. Further, the lead or electrode(s) may be the same type of use for spinal cord stimulation (e.g., cylindrical or paddle-type leads).

[0317] As mentioned above, a proximal end of each of the plurality of electrode lead wires may be located exterior to the patient's body when in use. Alternatively, the plurality or all of the electrode lead wires may be located interior to the patient’s body (or under the skin) when in use. The proximal end may include one or more deinsulated lengths for connection to an electrical connector in combination with the remainder of the electrode leads. The deinsulated portion may be located on any portion of the proximal portion of the lead located outside of the body. In an embodiment, the deinsulated portion may be located on one or multiple portions on the proximal end of the lead that is located partially or completely inside the body. In some embodiments, the distal end of each lead, which may be inserted directly into tissue, may also include a deinsulated length. In another embodiment, the deinsulated length(s) of lead forming the electrode(s) may be located at some distance proximal to the distal tip and anchor, which can be used to enable larger length of lead placement below the skin for anchoring. The deinsulated length may act as the stimulation electrode. In an embodiment, the lead may include multiple deinsulated lengths, with none, some, or all lengths separated by an insulated length. In an embodiment, the lead may have more than one stimulation electrode. At least a portion of the deinsulated length may be bent or otherwise deformed into a barb or anchor. This may anchor the electrode in the selected tissue. At least a portion of the insulated length may be bent or otherwise deformed into a barb or anchor. A taper, made from silicone adhesive or the like, may be formed between the deinsulated portion(s) of the lead and the insulated portion(s) of the lead to reduce stress concentration. The electrode may be placed anywhere along the length of the lead; the present teachings are not limited to the aforementioned locations. The electrode may be a conductive contact connected (e.g., welded, via adhesive) to the lead. Alternatively, the lead may be threaded (e.g., like a screw), and may be inserted into the tissue (e.g., pushed, deployed, screwed), which will mechanically secure the lead in the tissue in or around the target nerve in the back.

[0318] Each of the plurality of percutaneous electrodes may be inserted (e.g., injected, placed) through the skin and into a patient’s tissue. The associated electrode lead may exit the patient percutaneously (i.e., through the skin), for connection to the stimulation pulse generator. Each of the electrodes may be implanted or otherwise inserted into the select tissues by use of a needle. The needle may be straight or may be hooked or curved (e.g., bent). As an example, a curved introducer needle may be used to increase the length of lead under the skin (e.g., to prevent dislodgement) or to navigate anatomical features of the body (e.g., curve around bone, muscle, nerves, arteries). The curved introducer improves the ease of lead insertion by resembling the curvature of the desired lead placement path (e.g., mimicking the curvature of the spine at the desired target level), and may be used to minimize risks of puncture or perforation of sensitive anatomical structures (e.g., pleura, spinal canal, blood vessels, bone, etc.). The curved introducer may be used in a convex (e.g., curved outward) or concave (e.g., curved inward) approach, as needed for lead placement in the target anatomical region. A curved introducer is an improvement over the prior art of straight needle introducers, which must be carefully positioned to avoid sensitive anatomical structures (e.g., resulting in a longer procedural time) and may not result in an ideal lead placement trajectory. The curved introducer may be used to both place more lead under the skin to minimize dislodgement and place the lead through a path that avoids muscle planes to minimize shear stresses on the implanted electrode and lead. Exemplary embodiments of the use of a curved introducer to place a peripheral nerve stimulation in the back for pain relief are shown in FIG. 29, demonstrating use in the area of the lumbar curve of the spine, the cervical curve of the spine, and the sacral curve of the spine and overcoming prior limitations of straight needle introducers, which can be difficult to use for lead insertion. The curved introducer needle can also be used to more easily insert a peripheral nerve stimulation lead along (e.g., parallel to) the curvature of the ribs, toward the paravertebral space for the stimulation of peripheral spinal nerves (e.g.,avoiding puncture of the pleura or abdominal cavity). The curved introducer may be combined with any of the above-mentioned lead designs, including those with deinsulated electrode portions offset proximally from the distal end of the lead, in order to combine methods to optimally place the electrode near the target nerve or nerves. Alternatively, the lead may be inserted using other hollow tubes (e.g., cannula, catheter) or may be “shot” out of a device at sufficiently high speeds such that a rigid structure (e.g., needle) is not needed to penetrate the skin. Alternatively, the lead may be introduced into or through a vessel (e.g., vein, artery) or other structure (e.g., spinal canal, epidural space). Alternatively, the lead itself may be rigid, enabling the lead to be insertable into the tissue without another object (e.g., a needle). Alternatively, or in addition, tissues may be surgically exposed for implantation or minimally invasive techniques such as arthroscopy may be used. Alternatively, multiple electrodes may be on an array (e.g., paddle electrode, cylindrical electrode, array of needles, etc.). Once all of or some of or at least one of the electrodes are implanted as desired, their proximal ends may be crimped (e.g., attached) into a common connector that may mate with the cable assembly. The cable assembly may be, in turn, connected to the pulse generator through the connection socket. Alternatively, the electrodes may be connected directly to the stimulator. Alternatively, each electrode may be connected to an individual connector. Alternative means of securing the leads to the connector may also be used (e.g., magnetic, adhesive). Alternatively, multiple electrodes may be connected to an individual connector. Alternatively, multiple leads may be connected to an individual connector expanding the number of total leads and / or electrodes where stimulation can be delivered with one stimulation system. Alternatively, the proximal ends of the leads may terminate on a plug (e.g., banana plug, BNC plug, or other suitable connection) that can be connected to the stimulator either directly or via a connector. In an embodiment, one connector can provide connection between one system and one lead. In an embodiment, one connector can provide connection between one system and more than lead(e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more leads) that target the same or different nerves or nerve branches. A single multicontact connector with multiple leads can provide the same or different parameters (e.g., pulse duration, amplitude, frequency, intensity) to each lead.

[0319] The present percutaneous stimulation system may allow for precise selection of nerve stimulation and use of two or more stimulation electrodes and channels. Alternatively, a system may use one stimulation electrode. The present system may use two or more electrodes, each connected to an independent electrode stimulation channel, and a single reference electrode that may be a percutaneous, surface electrode, the case of the stimulator (if implanted), or an implanted electrode. Alternatively, there may be more than one reference electrode, and each stimulation channel may have its own reference electrode. The electrode stimulation channels may or may not be independent (i.e., the same stimulation may be delivered to multiple channels at once).

[0320] In an embodiment, the stimulator may be set within a range of intensities including amplitude and pulse width (e.g., any combination of two whole integers or nonintegers between 0.1 and 30.0 mA and, separately, between 10 and 200 microseconds, so as to form lower and upper limits for each) and frequencies (e.g., any combination of two whole integers or non-integers between 1 and 150 Hertz, again forming lower and upper limits to the ranges contemplated and expressly disclosed herein). It should be understood, however, that these intensities are merely exemplary, and the present teachings are not limited to such. In another embodiment, the stimulator may be set within a range of intensities including amplitude and pulse width (e.g., any combination of two whole integers or non-integers between 0.1 and 30.0 mA (or 0.1 and 20mA, or 0.1 and 40 mA, or 0.1 and 50 mA, or 0.1 and 60 mA, or 0.1 and greater than 30 mA) separately, between 10 and 200 microseconds (or between 5 and 300 microseconds, between 10 and 400 microseconds, between 10 and 500 microseconds, between 10 and greater than 200 microseconds, etc), so as to form lower andupper limits for each) and frequencies (e.g., any combination of two whole integers or nonintegers between 1 and 150 Hertz (or between 1 and 200 Hertz, between 1 and 300 Hertz, between 1 and 600 Hertz, between 1 and 1000 Hertz, between 1 and 10000 Hertz, between 1 and 20000 Hertz, between 1 and greater than 20000 Hertz) again forming lower and upper limits to the ranges contemplated and expressly disclosed herein).

[0321] A stimulus pulse train T may include a plurality of successive stimulus pulses P. The amplitude of stimulus pulse P may be current-regulated and / or voltage-regulated. It may also be biphasic (i.e., comprises a cathodic charge phase (Qc) and an anodic charge-phase (Qa)). Alternatively, the stimulus pulse may be monophasic (i.e., comprises only a cathodic charge phase or anodic charge phase) or contain more than 2 phases. The magnitude of the cathodic charge phase(s) may be equal the magnitude of the anodic charge phase(s). The current-regulated, biphasic pulses P may provide for consistent muscle recruitment along with minimal tissue damage and electrode corrosion. As an alternative or addition, a stimulus pulse may be regulated by other parameters (e.g., voltage-regulated, charge-regulated).

[0322] Each pulse P may be defined by an adjustable current or amplitude I (or voltage for voltage-regulated, or charge for charge-regulated, etc.) and an adjustable pulse duration PD. The pulse frequency PF may also be adjustable. Further, the current I, pulse duration PD, and pulse frequency PF may be independently adjustable for each stimulation channel E. The amplitude of the anodic charge phase (Qa) may be fixed or adjusted as desired.

[0323] Pulse "ramping" may be used at the beginning and / or end of each stimulation pulse train T to generate smooth muscle contraction, but other methods may be used as well. Ramping is defined herein as the gradual change in cathodic pulse charge magnitude by varying at least one of the current I and pulse duration PD. As mentioned, each of the plurality of stimulation leads / electrodes 40, 50 may be connected to the pulse generator circuit 60 via a stimulation pulse channel E. Two stimulation pulse channels El and E2 may be provided toindependently drive up to two electrodes 50. Stimulation pulse trains transmitted on each channel El and E2 may be transmitted within or in accordance with a stimulation pulse train envelope B1-B2, respectively. The characteristics of each envelope B1-B2 may be independently adjustable by a clinician for each channel E1-E2. Referring particularly to the envelope B2 for the channel E2, each envelope B 1 -B2 may be defined by a delay or "off phase PDO where no pulses are delivered to the electrode connected to the subject channel, i.e., the pulses have a pulse duration PD of 0. Thereafter, according to the parameters programmed into the circuit 60, the pulse duration PD of each pulse P is increased or "ramped-up" over time during a "ramp-up" phase PD1 from a minimum value (e.g., 5 psec) to a programmed maximum value. In a pulse duration "hold" phase PD2, the pulse duration PD remains constant at the maximum programmed value. Finally, during a pulse duration "ramp-down" phase PD3, the pulse duration PD of each pulse P may be decreased over time to lessen the charge delivered to the electrode 50. Further, it is possible to "ramp-up" and "ramp-down" for zero seconds, which indicates that there is no ramping. This "ramping-up" and "ramping-down" is illustrated even further with reference to the stimulation pulse train T which is provided in correspondence with the envelope B2 of the channel E2. In accordance with the envelope B2, the pulse P of the pulse train T first may gradually increase in pulse duration PD, then may maintain the maximum pulse duration PD for a select duration, and finally may gradually decrease in pulse duration PD.

[0324] As mentioned, the current I, pulse duration PD, pulse frequency PF, and envelope Bl -B2 may be adjustable for every stimulation channel E, independently of the other channel. The waveform shape (e.g., rectangular, exponential, ramp; pre-pulse, post-pulse) and channel synchrony (i.e., when stimulation through each channel starts and stops with respect to the other channels) may also be adjustable. The stimulation pulse generator circuit 60 may be pre-programmed with one or more stimulation patterns, which maa allow a patient to selectthe prescribed one of the patterns as required or otherwise desired during therapy. The pulse train, however, does not have to be constant (e.g., frequency may vary). Additionally, the ramping parameters may be adjusted (e.g., off time, ramp up time, ramp down time, and hold time). In some embodiments, the pulse generator may include at least two stimulation pulse channels E. The stimulation pulse trains T of each channel E may be sequentially or substantially simultaneously transmitted to their respective electrodes 50. In one embodiment, the pulse frequency PF may be adjustable within the range of approximately 1 Hz to approximately 100 Hz, the cathodic amplitude PA may be preferably adjustable within the range of approximately 0.1 mA to approximately 100 mA, and the pulse duration PD may be preferably adjustable in the range of approximately 1 psec to approximately 500 psec delivered by the circuit 60.

[0325] The stimulating frequency may be selected from a range of frequencies (e.g., 1- 100 Hz, 1-300 Hz, 1-lOOOHz, l-1200Hz, l-1500Hz, 1- 10000Hz, l-20000Hz, 1-lOOOOOHz, 5- 100Hz, 5-150 Hz, 5-1200 Hz, 5-1500 Hz, 12-100Hz, 12-150Hz, 12-1500 Hz, 1200-10000Hz, 1200-20000Hz, 1500-10000 Hz, 1500-100000Hz, and / or 10,000- 100,000Hz). The frequency of stimulation may be constant or varying. In the case of applying stimulation with varying frequencies, the frequencies may vary in a consistent and repeatable pattern, in a random (or pseudo random) fashion, or a combination of repeatable and random patterns. Stimulation may consist of a single frequency delivered through a single lead, or one or more frequencies delivered by one or more leads (e.g., Frequency A from Lead A and Frequency B from Lead B). The different leads delivering different stimulation frequencies may be placed targeting the same or different peripheral or spinal nerves. In a non-limiting example, a stimulating lead may deliver 12 Hz stimulation to a medial branch of the dorsal ramus of a cervical spinal nerve to activate paraspinal musculature while a second stimulating lead may deliver 96 Hz or 100 Hz stimulation to the greater occipital nerve to activate large diameter sensory fibers such that thepain relieving effects of the system, device, and method incorporate the benefits of both motor (efferent) and sensory (afferent) fiber stimulation. It should be understood, however, that these frequencies are merely exemplary, and the present teachings are not limited to such. In a nonlimiting example, a stimulating lead may deliver 12 Hz (or 0.1-12 Hz, 12-48 Hz, 48-96 Hz, 96- 150 Hz, 150-500 Hz, 500-1000 Hz, 1000-15000 Hz) stimulation to a medial branch of the dorsal ramus of a cervical spinal nerve to activate paraspinal musculature while a second stimulating lead may deliver 96 Hz or 100 Hz (or 0.1-12 Hz, 12-48 Hz, 48-96 Hz, 96-150 Hz, 150-500 Hz, 500-1000 Hz, 1000-15000 Hz) stimulation to the greater occipital nerve to activate large diameter sensory fibers such that the pain relieving effects of the system, device, and method incorporate the benefits of motor (efferent) and / or sensory (afferent) and / or mixed (motor and sensory) fiber stimulation.

[0326] The stimulation pulse generator may include a microprocessor-based stimulation pulse generator circuit with a micro controller. Operational instructions or other information may be stored in non-volatile storage. Set stimulation therapy or patterns may be included in this storage. These therapies may be based upon generalized information such as information that may be gathered from radiographic evaluation in multiple dimensions along with selected stimulation. Ultimately patient specific information may be incorporated into the stimulation parameters in order to optimize the therapy for a particular individual application. Preferably, the nonvolatile memory may also provide storage for all patient-specific stimulation protocols. A real-time clock may be provided as part of the circuit.

[0327] The electrical stimulator current may pass between the selected electrodes and the reference electrode(s). A pulse duration timer may provide timing input as determined by the CPU to the pulse amplitude / duration controller to control the duration of each stimulation pulse. Likewise, the CPU may provide a pulse amplitude control signal to the circuit by way of the serial peripheral interface to control the amplitude of each stimulation pulse.

[0328] Each output channel may include independent electrical charge storage such as a capacitor that is charged to the high voltage through a respective current limiting diode. To generate a stimulation pulse, the microcontroller output circuit may provide channel select input data to switch component, as to the particular channel on which the pulse may be passed. Switch may close the selected switch accordingly. The microcontroller may also provide a pulse amplitude control signal into a voltage-controlled current source. As such, the pulse amplitude control signal may control the magnitude of the current, and the circuit may ensure that the current is constant at that select level as dictated by the pulse amplitude control input. For stimulation of one or more human nerves (e.g., afferent fibers in a peripheral nerve), the current may be within an approximate range of 1 mA-30 mA, 0.1 mA-30mA, or 1 mA-60mA, or 0.1 mA- 100mA. However, the present teachings are not limited to such range. Any appropriate range may be used with the present teachings.

[0329] Upon completion of the cathodic phase as controlled by the pulse duration control signal, the discharged capacitor may recharge upon opening of the formerly closed one of the switches. The flow of recharging current to the capacitor may result in a reverse current flow between the relevant electrode and the reference electrode, thus defining an anodic pulse phase. The current amplitude in the anodic pulse phase is limited, preferably to 0.5 mA, by the current limiting diodes. Of course, the duration of the anodic phase may be determined by the charging time of the capacitor, and current flow may be blocked upon the capacitor becoming fully charged. It should be recognized that the interval between successive pulses or pulse frequency may be controlled by the CPU directly through output of the channel select, pulse amplitude, and pulse duration control signals as described at a desired frequency.

[0330] Some embodiments may implement one or more (e.g., 1, 1-2, 3-6, 7-10, or more than 10) independent preprogrammed patterns. Embodiments may have one or more pulses occurring concurrently, simultaneously, alternating, overlapping, non-overlapping, randomly,interleaved, and the like. For each pattern, a stimulation session may be pre-programmed into the stimulator circuit by a clinician through use of the input device. Each session may have a maximum session duration of approximately 3, 6, 9, 12, or 24 hours, and a session starting delay. However, it should be understood that these parameters are merely exemplary and not exhaustive or exclusive.

[0331] The stimulus pulse train may include a plurality of successive stimulus pulses. A stimulus pulse may be current-regulated. It may also be biphasic (i.e., comprises a cathodic charge phase and an anodic charge-phase). Alternatively, the stimulus pulse may be monophasic (i.e., comprises only a cathodic charge phase or anodic charge phase), or contain more than 2 phases (e.g., 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 phases). The magnitude of the cathodic charge phase(s) may be equal to the magnitude of the anodic charge phase(s). The current-regulated, biphasic pulses may provide for consistent nerve fiber recruitment along with minimal tissue damage and electrode corrosion. Alternatively, or in addition to, a stimulus pulse may be regulated by other parameters (e.g., voltage-regulated, charge-regulated).

[0332] Each pulse may be defined by an adjustable current (or voltage for voltage- regulated, or charge for charge-regulated, etc.) and an adjustable pulse duration. The pulse frequency may also be adjustable. Further, the current, pulse duration, and pulse frequency may be independently adjustable for each stimulation channel. The amplitude of the anodic charge phase may be fixed, but may be adjusted if desired.

[0333] Stimulation pulse trains transmitted on a given channel may be transmitted within or in accordance with a stimulation pulse train envelope. The characteristics of each envelope may be independently adjustable by a clinician for each channel. Referring particularly to the envelope for the channel, each envelope may be defined by a delay or “off’ phase where no pulses are delivered to the electrode connected to the subject channel, i.e., the pulses have a pulse duration of 0.

[0334] As mentioned, the current, pulse duration, pulse frequency, and envelope may be adjustable for every stimulation channel, independently of other channels. The waveform shape (e.g., rectangular, exponential, ramp; pre-pulse, post-pulse) and channel synchrony (i.e., when stimulation through each channel starts and stops with respect to the other channels) may also be adjustable. The stimulation pulse generator circuit may be pre-programmed with one or more stimulation patterns, which may allow a patient to select the prescribed one of the patterns as required or otherwise desired during therapy. The pulse train, however, does not have to be constant (e.g., frequency may vary) and other parameters may also be adjusted (e.g., off time, hold time).

[0335] In some embodiments, the pulse generator may include more than one stimulation pulse channels. The stimulation pulse trains of each channel may be sequentially or substantially simultaneously transmitted to their respective electrodes. The pulse frequency for each may be adjustable within the range of approximately 0.1-12 Hz, 12-48 Hz, 48-96 Hz, 96-150 Hz, 150-500 Hz, 500-1000 Hz, 1000-15000 Hz; the cathodic amplitude may be preferably adjustable within the range of approximately 0.1-10 mA, 1-30 mA, and 1-100 mA; and, the pulse duration may be preferably adjustable in the range of approximately 1-50 psec, 1-100 psec, 1-300 psec, and 1-1000 psec delivered by the circuit.

[0336] In some embodiments, a pulse generator may contain two or more stimulating electrodes to one or more target nerves innervating region(s) of pain related to the spine. In such embodiments, the pulse generator may provide pulses with different frequencies for the two or more stimulating electrodes. In such embodiments, the frequencies may be variable within a range (e.g., 0.1-20 Hz, 20-100 Hz, 100-500 Hz, 500-15000 Hz) and independently selectable for each nerve target (i.e., any combination of frequencies could be selected depending on nerve target and use). For example, the pulse generator may provide pulses at different frequencies ranges (e.g., 0.1-20 Hz, 20-100 Hz, 100-500 Hz, 500-15000 Hz) to twoor more electrodes. In an embodiment, the electrical stimulation system may include two or more electrodes providing stimulation of different frequencies. In an embodiment, the electrical stimulation system may include multiple or a plurality of electrodes providing stimulation of different frequencies. In an embodiment, the electrical stimulation system may include at least two electrodes each providing stimulation of different frequencies (e.g., 0.1-20 Hz, 20-100 Hz, 100-500 Hz, 500-15000 Hz, greater than 15000 Hz). In an embodiment, the electrical stimulation system may include a first electrode and a second electrode, each providing stimulation of different frequencies (e.g., one embodiment could include use of 4-20 Hz for one electrode and 60-120 Hz for a second electrode). In an embodiment, one system containing two or more electrodes of differing frequencies may be used in order to recondition pain processing in the central nervous system. The two or more frequencies provided over two or more electrodes may be used to activate neural fibers that engage multiple mechanisms to provide pain relief, resulting in a synergistic effect on neural pathways and central pain processing, and more comprehensive relief (e.g., providing pain relief of one or multiple etiologies of pain in one or multiple locations of pain). In an embodiment, the system may include one or more electrodes that provide stimulation at lower frequencies (e.g., 1-4, 4-20, or 20-60 Hz) to target motor nerve fibers that result in cyclical muscle twitches and / or muscle contractions and indirectly activate proprioceptive afferent pathways. In an embodiment, the system may contain one or more electrodes that provide stimulation at higher frequencies (e.g., 60-120, 120-500, 50 - 1499, 20 - 1500, 20-2000, 20-20,000 Hz, and / or greater than 20,000 Hz) to directly activate afferent pathways. The different frequencies (e.g., a lower frequency and higher frequency, two lower frequencies, two higher frequencies, or any combination of lower and higher frequencies) may be provided in order to mimic the natural coordination between sensory and motor signals in the central nervous system and provide pain relief to systems disrupted by disease, trauma, overuse, or other maladaptive changes. Targeting bothsensory nerve responses may provide a continuous paresthesia over the region of pain and periodic motor nerve response to elicit a comfortable muscle twitch and / or contraction without unwanted fatigue. The two or more electrodes of differing frequencies may be placed near the same nerve or nerve branch, engaging in both indirect and direct afferent pathways. Alternatively, the two or more electrodes of differing frequencies may be placed at different nerves, providing more comprehensive relief. In an embodiment, the pulse generator may be external to the body, providing stimulation using two or more frequencies to electrodes that are percutaneously placed. In an embodiment, one system containing two or more electrodes with two or more frequencies may be permanently implanted at the target nerves in the back in order to provide continuous inputs that recondition the centrally maintained pain state. In another embodiment, the stimulation system may use two or more stimulating leads where one stimulating lead activates peripheral or spinal nerves in a way that produces the activation of muscles and the same or a different stimulating lead (e.g., a second lead) activates the same or different peripheral or spinal nerves to produce the activation of large diameter sensory fibers without the activation of muscles.

[0337] In one embodiment, the system may be a short-term, temporary system wherein the temporary or short-term treatment period may range from minutes to hours to days to weeks to months. By way of a non-limiting example, the short-term or temporary treatment period may be between approximately 21 and 30 days, or between approximately 56 and 60 days, or between 21 and 60 days, or between 30 and 60 days, or between 30 and 90 days, or between 60 and 120 days. In this embodiment, it may be advantageous to avoid permanent implantation of lead(s), pulse generator(s), and / or other system components because patients may achieve long-term sustained pain relief from a short-term treatment, obviating the need for permanent implantation and reducing the safety risks and financial costs associated with permanent implantation. The lead may be a temporary, removable, short-term, and / or non-permanentlyimplanted percutaneous lead that is flexible, coiled, self-anchoring, migration resistant, fracture resistant, and / or infection resistant, and the coiled structure may enable the lead to flex and bend when subjected to forces rather than migrate or fracture. The lead(s) may possess mechanical properties in terms of flexibility and fatigue life that provide an operating life free of mechanical and / or electrical failure, taking into account the dynamics of the surrounding tissue (e.g., stretching, bending, pushing, pulling, crushing, etc.). There may be one or more coils, with the coils composed of bundles of conductive wires (e.g., a plurality of strands of wire formed into a conductive bundle). Each of the conductive wires, as well as the coils, are wired (connected, placed) in parallel to the electrical stimulation / pulse generator to ensure that a fracture sustained in a single wire does not inhibit therapeutic pulses delivered by the lead as a whole. In this embodiment, the helical or open-coil structure of the lead is desirable such that the interstices of the coils will allow tissue ingrowth to secure better the lead within the patient’s body, thereby reducing lead migration. However, it is to be appreciated that it may be desirable to discourage the in-growth of connective tissue along its length or an applicable portion thereof so as not to inhibit its withdrawal at the end of its use. For example, tissue ingrowth may be discouraged through the use of a closed coil or non-coiled lead and / or the use of materials.

[0338] In this embodiment, one or more temporary, short-term, and / or removable lead(s) may be inserted percutaneously and electrically coupled (e.g., directly and / or using one or more connectors, couplers, cables, or other components or features) to an external pulse generator and may deliver stimulation for a temporary or short-term treatment period through the one or more leads independently (e.g., on one or more separate, independent stimulation channels or programs) or non-independently (e.g., wherein the one or more leads are electrically coupled and deliver the same stimulus or program). In embodiments of this percutaneous system, one or more surface electrode(s) may serve as the anode(s) (or returnelectrode(s)). The surface electrodes may be of a standard shape, or they may be modified as appropriate to fit the contour of the skin. When serving as a return electrode(s), the location(s) of the electrode(s) may not be critical and may be positioned anywhere in the general vicinity (e.g., on the shoulder, abdomen, lower back, or upper or lower extremity), provided that the current path does not cross parts of the body, through which stimulation could be harmful (e.g., the heart).

[0339] During the treatment period (e.g., three weeks, eight weeks, 60 days, 30 days), the treatment may reduce pain while stimulation is on and may lead to reduced pain while stimulation is off. The nerve stimulation and resulting muscle contractions may provide pain relief that may also persist after the treatment period (carryover effect) for several minutes to several years by modulating the central nervous system’s processing of pain. Thus, this temporary (e.g., four weeks) treatment may provide long-term pain relief at least as long as the treatment period itself (e.g., three weeks to one year). Further, this treatment may cause change to the nervous system that relieves pain.

[0340] Compared to individuals with healthy spines, patients with chronic spine pain have reduced function, health-related quality of life, and range of motion. When treatments reduce chronic spine pain, function, health-related quality of life, and range of motion improve. As a result, the reductions in chronic spine pain generated by the system may be expected to result in improvements in function and significant improvements in health-related quality of life and range of motion. When combined with other neck pain therapies, the system may enhance overall effectiveness. When physical function improves and the patient becomes more active, there will be increased daily muscle contractions in the area around the spine and around the lead, which will cause increased forces and cycling of forces on the lead. By aligning the lead with the muscle as taught in the present invention, the lead will be able to withstand the increased cycling produced by increased physical activity that results from treatment.

[0341] In alternative embodiments, the pulse generator may be implantable into a patient’s body and would generate stimulation in a similar fashion as described previously with an external stimulator. In such embodiments, the pulse generator may be implanted in any appropriate location of a patient’s body, including, without limitation, within the back, abdomen, legs, torso and the like. With an implantable pulse generator, both the generator and the electrodes (and leads, if applicable) may be placed underneath the skin. As a result, a programmer may communicate with the stimulator through the skin. Prior to placing the implantable pulse generator, a patient may use a percutaneous system as a trial.

[0342] In another embodiment, the system may be a long-term and / or permanently implanted system wherein the treatment period may be continuous and / or indefinite (i.e., the system is not intended to be removed) and individual stimulation sessions may be applied that range from minutes to hours to days to weeks to months to continuous or indefinite but the implanted lead and other system components are not removed or explanted in between individual stimulation sessions. By way of a non-limiting example, the system may deliver stimulation continuously for many years and / or indefinitely, or the system may deliver stimulation for any finite period or session or intermittent session or period consisting of seconds, minutes, or hours per day, or days per week, or weeks per month, or months per year in a repeating and regular or irregular cycle (e.g., any of the following and / or greater than the following and / or between a range of any combination of the following: 10 minutes per day, 15 minutes per day, 20 minutes per day, 30 minutes per day, 60 minutes per day, 2 hours per day, 3 hours per day, 4 hours per day, 5 hours per day, 6 hours per day, 7 hours per day, 8 hours per day, 9 hours per day, 10 hours per day, 11 hours per day, 12 hours per day, 1 day per week, 2 days per week, 3 days per week, 4 days per week, 5 days per week, 6 days per week, 7 days per week, 1 week per month, 2 weeks per month, 3 weeks per month, 4 weeks per month, 1 month per year, 2 months per year, 3 months per year, 4 months per year, 5 months per year, 6months per year, 7 months per year, 8 months per year, 9 months per year, 10 months per year, 11 months per year, 12 months per year, etc.) and this approach may also be applied, delivered, performed, and / or instructed over a duration of multiple days (e.g., 0-7 days, 0-14 days, 0-15 days, 0-30 days, 0-60 days, 60-180 days, greater than 180 days), weeks (e.g., 0-1 weeks, 1-4 weeks, 4-8 weeks, 4-16 weeks, greater or less than 16 weeks), months (e.g., less than 1 month, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, or greater than 12 months), years (e.g., less than 1 year, 1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, or greater than 10 years), and / or decades (tens) of years or more. In this embodiment, it may be advantageous to permanently implant lead(s), pulse generator(s), and / or other system components to provide patients with long-term sustained pain relief through the continuous and / or on-demand delivery of stimulation in situations where short-term stimulation does not or is unlikely to produce sustained relief. The lead may be an implanted, or long-term, or permanently implanted lead that is flexible, self-anchoring, migration resistant, fracture resistant, and / or infection resistant, and may have an open coil, closed coil, or non-coiled structure that enables the lead to flex and bend when subjected to forces rather than migrate or fracture. The lead(s) may possess mechanical properties in terms of flexibility and fatigue life that provide an operating life free of mechanical and / or electrical failure, taking into account the dynamics of the surrounding tissue (e.g., stretching, bending, pushing, pulling, crushing, etc.). There may be one or more open or closed coils, with the coils composed of bundles of conductive wires (i.e., a plurality of strands of wire formed into a conductive bundle). Each of the conductive wires, as well as the coils, are wired in parallel to the electrical stimulation / pulse generator to ensure that a fracture sustained in a single wire does not inhibit therapeutic pulses delivered by the lead as a whole.

[0343] In this embodiment, one or more implanted, long-term, and / or permanently implanted lead(s) may be inserted percutaneously and electrically coupled (e.g., directly and / or using one or more connectors, couplers, cables, or other components or features) to an implanted internal pulse generator (IPG) and may deliver stimulation for a long-term and / or indefinite treatment period through the one or more leads or electrodes independently (e.g., on one or more separate, independent stimulation electrodes, contacts, channels or programs) or non-independently (e.g., wherein the one or more leads and / or one or more electrodes or contacts are electrically coupled and deliver the same stimulus or program). In embodiments of this permanently implanted system, one or more electrodes or contacts on a lead and / or the IPG (i.e., the “case”) may serve as the anode(s) (or return electrode(s)). When serving as a return electrode(s), the location of the IPG may not be critical and may be positioned anywhere in the general vicinity (e.g., on the shoulder, abdomen, lower back, or upper or lower extremity), provided that the current path does not cross parts of the body through which stimulation could be harmful (e.g., the heart).

[0344] Patients may undergo implantation of a temporary system for a short-term, temporary stimulation treatment and / or may undergo implantation of a permanent system for a long-term or indefinite stimulation treatment. It may also be advantageous for patients to receive a short-term, temporary stimulation treatment as a short-term trial prior to implantation of a permanent stimulation system, wherein the short-term system delivers the same stimulation therapy as the permanent system and may provide the physician and / or patient with information, data, and / or predictive knowledge about the likelihood of achieving successful outcomes (e.g., reduced pain, increased function, reduced disability, etc.) from a permanently implanted system. The short-term system may preferably deliver the same stimulation therapy (e.g., deliver the same stimulation waveform and / or parameters; utilize a temporary, short-term percutaneous lead with similar electrode size, surface area, and / or other properties ordimensions as the permanently implanted lead). However, it should be recognized that the short-term percutaneous system may not necessarily or preferably deliver the same stimulation waveform and / or parameters as the permanently implanted system, and / or other components, properties, dimensions, specifications, or features of the short-term and permanently implanted systems may not be identical or similar. Completing a short-term trial with a temporary, non- permanently implanted system may be advantageous prior to implantation of a permanent system because it may reveal patients who are not likely to respond positively to stimulation (e.g., not likely to achieve satisfactory pain relief or other benefits from stimulation) and therefore can avoid the risks and costs of permanent implantation. A short-term trial that is extended (e.g., 60 days) compared to prior conventional system trials that are commonly 7-10 days in length can additionally identify patients who experience delayed response to stimulation and may have otherwise been ruled out of consideration for implantation of a permanent system due to a poor initial response in the first 7-10 days that later increases to provide patients with significant pain relief. Additionally, an extended short-term trial may identify delayed non-responders and may have otherwise been implanted with a permanent system due to a strong initial response in the first 7-10 days that later wanes due to, for example, accommodation, habituation, or loss of placebo effects, and require surgical revision and / or explantation of the permanent system.

[0345] The present system, device, method, and instructions for use of systems, devices, and methods place the stimulation lead such that the location of the exit site of the percutaneous lead, that is, the location on the skin where the lead is inserted and where the externalized portion of the lead exits the skin, is conducive to the application of bandaging materials that protect the exit site from contamination and reduce infection rates during the temporary treatment period. In a non-limiting example, the exit site of the percutaneous stimulating lead is located inferior (i.e., below) the hairline of the patient, and ideally at least3 -4cm below the hairline to enable the application of a bandage around the exit site without requiring modification to the hairline (e.g., hair cutting, clipping, shaving, etc.). In another embodiment, the exit site may be located at or below the hairline and some portion of hair may be cut, clipped, or otherwise shortened or removed to enable placement of a bandage (e.g., an occlusive bandage) over the exit site of the percutaneous stimulating lead while avoiding adhesion of the bandage to the hair. In another embodiment, the exit site may be placed at or cephalad to the hairline and the hair may be clipped, cut, or otherwise shortened or removed to facilitate the use of an adhesive bandage, and / or non-fabric adhesive bandages (e.g., liquid bandage, skin glue, cyanoacrylate, 2-octyl cyanoacrylate, Dermabond, etc.) may be used to seal the exit site and protect against infection without requiring the hair to be removed, clipped, or cut.

[0346] In another non-limiting example, the exit site of the percutaneous stimulating lead is superior or cephalad to the waistline of a patient’s clothes and / or undergarments, and ideally at least 3 -4cm superior or cephalad to the waistline or waistband or a patient’s clothes, to enable application of a bandage over or around the exit site without compromising the ability of the bandage to adhere to the skin and protect the lead exit site (e.g., by causing discomfort under a waistband, or rubbing or friction from the waistband that disrupts bandage adhesion, etc.). In another non-limiting example, the exit site of the percutaneous lead is superior or cephalad to the buttocks (e.g., the upper boundary of the gluteus maximum, gluteaus, medius, and / or gluteus minimus, and / or at or cephalad to the iliac crest, and / or at or above the level of the waistband of clothing as worn by an individual patient) such that the lead can be placed targeting the appropriate or desired nerve target without placement of a bandage in, on, across, or near the intergluteal cleft. In an embodiment, the exit site is located outside of any region of sensitive skin, such as where there is a rash, sunburn, or otherwise allodynic skin including sensitivity caused by the pain condition being treated by the stimulation.

[0347] In a non-limiting example, the introducer needle that delivers the electrode to the target location may be of a fixed length. In this example, orientating the needle and lead to align with the musculoskeletal system may not be possible. In this example, primarily aligning the needle, lead, and / or electrode with the orientation of the muscle bundle (e.g., the longitudinal axis of the lead is within 5, 10, 15, 20, 25, 30, 35, 40, 45 degrees parallel to the axis of the muscle bundle) enables delivery of therapeutic stimulation while avoiding fracture, migration, and dislodgment (FIG. 30). In a non-limiting example, the percutaneous introducer needle that delivers the stimulating lead to its target location may not be curved, bent, or angled such that the deployment of the lead from the introducer needle may be compromise...

Claims

CLAIMSWhat is claimed is:

1. A method of peripheral nerve stimulation, the method comprising: inserting a lead into a musculoskeletal system body region; orienting the lead relative to the musculoskeletal system body region wherein the lead can withstand multiple forces and movements caused by electrical stimulation when a longitudinal axis of the lead is aligned with a direction of a net force and movement by the musculoskeletal system body region; causing a reversible change in a shape of the lead in one or more dimensions in response to orienting the lead; avoiding lead fracture or migration of the lead; and preventing interruption of therapeutic delivery of electrical stimulation to a nerve through the lead.

2. The method of claim 1 further comprising operatively coupling an electrical stimulation device to the lead and applying electrical stimulation via the electrical stimulation device through the lead.

3. The method of claim 1, wherein the lead comprises one or more electrodes integrally formed on the lead, wherein the one or more electrodes are positioned proximal to a region of pain and configured to deliver electrical stimulation to at least one nerve or nerve branch that innervates the region of pain.

4. The method of claim 3, wherein the electrical stimulation selectively activates target nerve fibers in the at least one nerve.

5. The method of claim 4, wherein the activation of target nerve fibers produces tingling sensations in the region of pain.

6. The method of claim 5, wherein the tingling sensations comprise at least one of paresthesia or muscle activation.

7. The method of claim 3, further comprising orienting the lead to position the one or more electrodes remote from the nerve.

8. The method of claim 3, wherein the at least one nerve comprises one or more of: spinal nerves, spinal nerve roots, medial, lateral, or other branches of dorsal or ventral rami, gluteal nerve and branches, cluneal nerve and branches, superior cluneal nerve and branches, middle cluneal nerves and branches, occipital nerves and branches rami communicantes, sympathetic chain, dorsal root ganglion.

9. The method of claim 8, wherein the at least one nerve is targeted in a paravertebral space.

10. The method of claim 8, wherein the at least one nerve is targeted in a spinal region but outside a paravertebral space.

11. The method of claim 8, wherein the at least one nerve lies in cervical, thoracic, lumbar, and / or sacral spinal regions.

12. The method of claim 4, wherein selective activation of target nerve fibers modulates central neural processing.

13. The method of claim 12, wherein modulation of central neural processing provides pain relief by reconditioning maladaptive pain processing in CNS.

14. The method of claim 13, wherein the reconditioning of maladaptive pain processing occurs during a temporary stimulation treatment period without use of a permanently implanted lead.

15. The method of claim 14, wherein the reconditioning of maladaptive pain processing during a temporary stimulation treatment period produces durable pain relief that outlasts a stimulation treatment period.

16. The method of claim 11, wherein modulation of central neural processing is achieved without blocking of transmission of neural signals from a periphery.

17. The method of claim 1, wherein pain relief is produced without or without requiring targeted or regenerative changes in stability of a spine, musculature, or connective tissues.

18. The method of claim 1, wherein pain relief is produced without providing or requiring mechanical stability.

19. The method of claim 1, wherein pain relief is produced without directly strengthening, rehabilitating, or stabilizing, or requiring strengthening, rehabilitation, or stabilization of paraspinal muscles.

20. The method of claim 1, wherein pain relief is produced without or without requiring functional improvement.

21. The method of claim 1, wherein pain relief is produced without functional improvement.

22. The method of claim 1, wherein the lead is aligned with force-producing structures of a musculoskeletal system to minimize forces produced by muscle, connective tissue, or other tissues.

23. The method of claim 22, wherein the lead is aligned with a force vector of a muscle it passes through.

24. The method of claim 22, wherein the lead is placed in or near a midbelly of a muscle and avoids a boundary of the muscle.

25. The method of claim 22, wherein the lead passes through more than one muscle and is oriented to be in line with a muscle that produces a highest force relative to any other muscles the lead passes.

26. The method of claim 22, wherein placement of the lead does not align with a force vector of the muscle it passes through.

27. The method of claim 26, wherein the lead is placed substantially parallel to a forceproducing structure of a musculoskeletal system to avoid shearing forces, bending forces, compressive forces, and tensile forces.

28. The method of claim 26, wherein the lead is placed such that a longitudinal axis of the lead is within 30 degrees of parallel to a net force vector of the muscles that the lead intersects.

29. The method of claim 26, wherein the lead is placed such that a longitudinal axis of the lead is within 30 degrees parallel to direction of motion of the muscles that the lead intersects.

30. The method of claim 22, wherein the reversibility of changes in shape of the lead is conferred by at least one elastic portion of the lead that is configured to stretch and return to its original shape in response to forces placed on it by surrounding tissues.

31. The method of claim 30, wherein the lead is placed such that an elastic portion of the lead is within 30 degrees parallel to a net force vector of the muscles that the lead intersects.

32. The method of claim 30, wherein placement of the lead is such that an elastic portion of the lead is within 30 degrees parallel to direction of motion of the muscles that the lead intersects.

33. The method of claim 22, wherein an orientation of lead minimizes a difference between an angle of trajectory of the lead and an angle of the muscles that the lead intersects.

34. The method of claim 22, wherein an orientation of the lead orientation minimizes a number of muscles intersected by the lead.

35. The method of claim 22, wherein an orientation of the lead orientation minimizes tensile forces, shear forces, compressive forces, and / or bending forces acting on the lead.

36. The method of claim 22, wherein the lead is aligned with a musculoskeletal system to minimize damage to the lead from detrimental effects of muscle bulging, muscle rotation,muscle gearing, or combinatory effects from an interaction between the muscles and other structures.

37. The method of claim 22, wherein an orientation of the lead avoids contact with sensitive structures.

38. The method of claim 22, wherein an orientation of the lead avoids contact with epidural space, arteries, and direct contact with nerves.

39. The method of claim 22, wherein an orientation of the lead avoids contact with bony structures.

40. The method of claim 22, wherein an orientation of the lead avoids impact of muscle forces and movement maintaining a desired therapeutic distance away from the nerve.

41. The method of claim 22 further comprising using a biophysical model to prescribe an alignment of the lead relative to a muscle, fascial planes, or other tissue structures or planes through which the lead passes or within which the lead is placed.

42. The method of the claim 22, wherein an orientation of the lead enables percutaneous lead placement wherein a skin exit site and required bandage are located at a predetermined location.

43. The method of claim 42, wherein the predetermined bandage location is above buttocks and below hairline.

44. The method of claim 43, wherein the predetermined bandage location is above a waistband of clothing worn on the body.

45. The method of claim 44, wherein an orientation of the lead enables percutaneous lead placement such that a placement procedure and lead exit site avoid areas sensitive to allodynia.

46. The method of claim 1, wherein the lead reversibly changes in shape or length in response to forces in the body avoid migration, fracture, movement, or displacement of the lead.

47. The method of claim 46, wherein a portion of the lead reversibly changes in shape or length in response to forces in the body avoiding migration, fracture, movement, or displacement of the lead.

48. The method of claim 47, wherein another portion of the lead is stiff and does not change shape in response to forces in the body.

49. The method of claim 46, wherein the lead is a flexible, open-coiled lead that coils and uncoils in one or more directions in response to changes in force and / or length.

50. The method of claim 49, wherein interstices of the coils allow tissue ingrowth to secure the lead within the body.

51. The method of claim 46, wherein the lead is a non-coiled lead that stretches in one or more directions in response to changes in force and / or length.

52. The method of claim 46, wherein the lead changes diameter in response to changes in force and / or movement.

53. The method of claim 46, wherein the lead is percutaneous and secured to skin.

54. The method of claim 46, wherein the lead is fully implanted wherein securement to skin is not required.

55. The method of claim 46, wherein orientation and path of the lead is configured so that movement of surrounding tissues causes the lead to deform in one or more planes with respect to the body.

56. The method of claim 46, the orientation and path of the lead is configured to limit undesirable deformation of the lead in one or more other planes with respect to the body.

57. A method of stimulating a peripheral nerve to provide pain relief, the method comprising: percutaneously inserting a lead into a region of a body wherein the lead is aligned with a direction of net force and movement by a musculoskeletal system in the region of the body, wherein the alignment mitigates against lead fraction or migration; and preventing interruption of therapeutic delivery of electrical stimulation to a nerve.

58. The method of claim 57 further comprising applying electrical stimulation through an electrical stimulation device operatively coupled to the lead.

59. The method of claim 58, wherein the lead comprises one or more electrodes integrally formed on the lead, wherein the one or more electrodes are configured to be positioned proximal to a region of pain to deliver electrical stimulation to at least one nerve or nerve branch that innervates the region of pain.

60. The method of claim 58, wherein the electrical stimulation selectively activates target nerve fibers in the nerve.

61. The method of claim 60, wherein the activation of target nerve fibers produces comfortable sensations in the region of pain.

62. The method of claim 61, wherein the comfortable sensations comprise at least one of paresthesia or muscle activation.

63. The method of claim 59 further comprising orienting the lead to position the one or more electrodes remote from a target nerve.

64. The method of claim 59, wherein the at least one nerve comprises spinal nerves, spinal nerve roots, medial, lateral, or other branches of a dorsal or ventral rami, gluteal nerve and branches, cluneal nerve and branches, superior cluneal nerve and branches, middle cluneal nerves and branches, occipital nerves and branches rami communicantes, sympathetic chain, or dorsal root ganglion.

65. The method of claim 64, wherein the at least one nerve is targeted in a paravertebral space.

66. The method of claim 64, wherein the at least one nerve is targeted in a spinal region but outside a paravertebral space.

67. The method of claim 64, wherein the at least one nerve lies in cervical, thoracic, lumbar, and / or sacral spinal regions.

68. The method of claim 60, wherein the selective activation of target nerve fibers modulates central neural processing.

69. The method of claim 68, wherein the modulation of central neural processing provides pain relief by reconditioning maladaptive pain processing in a CNS.

70. The method of claim 69, wherein reconditioning of maladaptive pain processing occurs during a temporary stimulation treatment period without use of a permanently implanted lead.

71. The method of claim 70, wherein reconditioning of maladaptive pain processing during a temporary stimulation treatment period produces durable pain relief that outlasts the temporary stimulation treatment period.

72. The method of claim 57, wherein modulation of central neural processing is achieved without requiring blocking of transmission of neural signals from a periphery.

73. The method of claim 57, wherein pain relief is produced without targeted or regenerative changes in stability of a spine, musculature, or connective tissues.

74. The method of claim 57, wherein pain relief is produced without providing mechanical stability.

75. The method of claim 57, wherein pain relief is produced without directly strengthening, rehabilitating, or stabilizing paraspinal muscles.

76. The method of claim 57, wherein pain relief is produced without functional improvement.

77. The method of claim 57, wherein the lead is aligned with force-producing structures in a musculoskeletal system to minimize forces produced by muscle, connective tissue, or other tissues.

78. The method of claim 77, wherein the lead is aligned with a force vector of the muscle it passes through.

79. The method of claim 77, wherein the lead is placed in or near a midbelly of the muscle and avoids a boundary of the muscle.

80. The method of claim 77, wherein the lead passes through more than one muscle and is oriented to be in line with a muscle that produces a highest force.

81. The method of claim 77, wherein placement of the lead does not align with a force vector of the muscle it passes through but is aligned while navigating other issues.

82. The method of claim 81, wherein the lead is placed generally parallel to a forceproducing structure of the musculoskeletal system to avoid shearing forces, bending forces, compressive forces, and tensile forces.

83. The method of claim 81, further comprising placing the lead wherein a longitudinal axis of the lead is within 30 degrees parallel to a net force vector of the muscles that the lead intersects.

84. The method of claim 81, further comprising placing the lead wherein a longitudinal axis of the lead is within 30 degrees parallel to direction of motion of the muscles that the lead intersects.

85. The method of claim 82, wherein the lead is orientated to minimize a difference between an angle of a lead trajectory and an angle of the muscles that the lead intersects.

86. The method of claim 82, wherein the lead is orientated to minimize a number of muscles intersected by the lead.

87. The method of claim 82, wherein the lead is orientated to minimize a tensile forces, shear forces, compressive forces, and / or bending forces acting on the lead.

88. The method of claim 87, wherein minimization of tensile, shear, compressive, and / or bending forces increases a lifespan of the lead.

89. The method of claim 82, wherein minimization of tensile, shear, compressive, and / or bending forces increase a lifespan of the lead by avoiding lead fracture.

90. The method of claim 77, wherein the lead is aligned with a musculoskeletal system to minimize damage to the lead from detrimental effects of muscle bulging, muscle rotation, muscle gearing, or combinatory effects from an interaction between muscles and other structures.

91. The method of claim 77, wherein the lead orientation avoids contact with sensitive structures.

92. The method of claim 77, wherein the lead orientation avoids contact with bony structures.

93. The method of claim 77, wherein orientation of the lead avoids an impact of muscle forces and movement that would displace the one or more electrodes away from a target nerve.

94. The method of claim 77, wherein results of a biophysical model prescribe alignment of the lead relative to muscles, fascial planes, or other tissue structures or planes through which the lead passes or within which the lead is placed.

95. The method of the claim 77, wherein the lead orientation enables percutaneous lead placement such that a skin exit site and required bandage are located at a predetermined location.

96. The method of claim 95, wherein the predetermined location is above buttocks and below hairline.

97. The method of claim 95, wherein the predetermined location is above a waistband of clothing worn on the body.

98. The method of claim 95, wherein orientation of the lead enables percutaneous placement such that a lead exit site avoids areas sensitive to allodynia.

99. The method of claim 57, wherein the lead reversibly changes in shape or length in response to forces in the body to avoid migration, fracture, movement, or displacement of the lead.

100. The method of claim 99, wherein at least one portion of the lead reversibly changes in shape or length in response to forces in the body to avoid migration, fracture, movement, or displacement of the lead.

101. The method of claim 100, wherein another portion of the lead is stiff and does not change shape in response to forces in the body.

102. The method of claim 98, wherein the lead is a flexible, open-coiled lead that coils and uncoils in one or more directions in response to changes in force and / or length.

103. The method of claim 102, wherein interstices of the coils allow tissue ingrowth to secure the lead within the body reducing lead migration.

104. The method of claim 103, wherein the lead is a non-coiled lead that stretches in one or more directions in response to changes in force and / or length.

105. The method of claim 104, wherein the lead changes diameter in response to changes in force and / or movement.

106. The method of claim 98, wherein the lead is percutaneous and secured at skin.

107. The method of claim 98, wherein the lead is fully implanted such that securement at skin is not required.

108. The method of claim 98, wherein the orientation and path of the lead is selected so that movement of surrounding tissues causes the lead to deform in one or more planes with respect to the body.

109. The method of claim 98, wherein an orientation and path of the lead is selected to limit deformation of the lead in one or more other planes with respect to the body.

110. The method of claim 57, wherein the lead is placed in a highly mobile region of the body.

111. The method of claim 110, wherein the highly mobile region of the body is a cervical spinal region.

112. The method of claim 98, wherein the lead is inserted into the body with an introducer needle.

113. The method of claim 112, wherein the introducer is curved to increase a length of lead introduced under skin.

114. The method of claim 112, wherein the introducer is curved to enable a lead trajectory to navigate anatomical features of the body.

115. A method of peripheral nerve stimulation, the method comprising: inserting a lead into a musculoskeletal system body region; causing a reversible change in a shape of the lead in one or more dimensions in response to forces applied on the lead; orienting the lead such that a longitudinal axis of the lead is aligned with a direction of a net force and movement by the musculoskeletal system body region; and preventing interruption of therapeutic delivery of electrical stimulation to a nerve through the lead.

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